TW202210505A - Antibodies against sars-cov-2 - Google Patents

Abstract

The instant disclosure provides antibodies and antigen-binding fragments thereof that can bind to a SARS-CoV-2 antigen and, in certain embodiments, are capable of potently neutralizing a SARS-CoV-2 infection. Also provided are polynucleotides that encode antibodies and antigen-binding fragments, vectors, host cells, and related compositions and uses, including for preventing, treating, and diagnosing an infection by SARS-CoV-2 or another coronavirus.

Description

Antibody against SARS-COV-2

Statement Regarding Sequence Listing

The Sequence Listing pertaining to this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into this specification. The name of the text file containing the sequence listing is 930585_409WO_SEQUENCE_LISTING.txt. The text file generated on May 7, 2021 is approximately 489 KB and submitted electronically via EFS-Web.

The present invention relates to antibodies against SARS-COV-2.

Background of the Invention

A novel betacoronavirus emerged in Wuhan, China in late 2019. As of May 2, 2021, approximately 152 million cases of infection with this virus (known as SARS-CoV-2 and other names such as Wuhan coronavirus) have been confirmed worldwide, and approximately 3.195 million deaths have been reported. There is a need for therapy to prevent or treat SARS-CoV-2 infection.

According to an embodiment of the present invention, an antibody or an antigen-binding fragment thereof is specially proposed, which comprises a heavy chain variable domain (VH) and a light chain variable domain (VL), and the heavy chain variable domain (VH) comprises A CDRH1, a CDRH2 and a CDRH3, and the light chain variable domain (VL) comprises a CDRL1, a CDRL2 and a CDRL3, wherein: (i) the CDRH1 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NO.: 400, 23, 33, 43, 53, 63, 75, 85, 97, 107, 120, 130, 140, 147, 160, 170, 174, 183, 190, 199, 209, 219, 229, 241, 255, 265, 275, 285, 299, 313, 323, 333, 370, 380, 390, 410, or including one , a sequence variant of two or three acid substitutions, one or more of these substitutions optionally being a conservative substitution and/or a substitution to a germline encoded amino acid; (ii) the CDRH2 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NO.: 401, 24, 34, 44, 54, 64, 76, 86, 98, 108, 121, 131, 141, 148, 151, 161, 171, 184, 200, 210, 220, 230, 242, 256, 266, 276, 286, 300, 314, 324, 334, 352, 360, 362, 364, 366, 371, 381, 391, 411, 421, 431, 436, 446, 456, 466, 476, 486, 496, 506, 516, 526, 536, 546, 556, 566, 576, 586, 596, 606, 616, 625, 632, 635, 637, 639, 641, 643, 645, 647, 649, 651, 653, 655, 657, 659, 661, 663, 665, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685 and 694, or a sequence variant thereof comprising one, two or three amino acid substitutions, one or more of which are optionally a conservative substitution and/or a Substitution of one of the germline encoded amino acids; (iii) the CDRH3 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NO.: 766, 25, 35, 45, 55, 65, 77, 87, 99, 109, 122, 132, 142, 149, 162, 164, 165, 172, 176, 177, 179, 180, 185, 187, 188, 201, 211, 221, 231, 243, 257, 267, 277, 287, 301, 315, 325, 335, 354, 372, 382, 392, 412, 422, 432, 437, 447, 457, 467, 477, 487, 497, 507, 517, 527, 537, 547, 557, 567, 577, 587, 597, 607, 617, 627, 633, 695, 751, 753, 755, 757, 760, 763, 765 and 402, or a sequence variant thereof comprising one, two or three amino acid substitutions, and the like One or more of the substitutions are optionally a conservative substitution and/or a substitution to a germline encoded amino acid; (iv) the CDRL1 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NO.: 404, 27, 37, 47, 57, 67, 79, 89, 101, 111, 124, 134, 144, 152, 155, 156, 158, 159, 166, 181, 192, 203, 213, 223, 233, 245, 259, 269, 279, 289, 303, 317, 327, 337, 356, 374, 384, 394, 414, 424, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 687 and 697, or a sequence variant comprising one, two or three amino acid substitutions, one or more of which are optionally a conserved substitution and/or a change to a germline encoded amino acid a replacement; (v) the CDRL2 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NO.: 405, 28, 38, 48, 58, 68, 80, 90, 102, 112, 125, 135, 145, 153, 167, 182, 193, 204, 214, 224, 234, 246, 260, 270, 280, 290, 304, 318, 328, 338, 375, 385, 395, 415, 425, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 688 and 698, or including one, two or three A sequence variant of amino acid substitutions, one or more of which are optionally a conservative substitution and/or a substitution to a germline-encoded amino acid; and/or (vi) the CDRL3 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NO.: 406, 29, 39, 49, 59, 69, 81, 91, 103, 113, 126, 136, 146, 169, 195, 197, 205, 215, 225, 235, 247, 261, 271, 281, 291, 305, 319, 329, 339, 358, 376, 386, 396, 416, 426, 441, 451, 461, 471, 481, 491, 501, 511, 521, 531, 541, 551, 561, 571, 581, 591, 601, 611, 621, 689, 699, 745 and 747, or including one, two a sequence variant of one or three amino acid substitutions, one or more of which is optionally a conservative substitution and/or a substitution to a germline-encoded amino acid, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention provides antibodies and antigen-binding fragments that bind to SARS-CoV-2 coronaviruses (eg, SARS-CoV-2 surface glycoproteins and/or RBDs described herein, in SARS-CoV-2 virions and/or or expressed on the surface of cells infected by the SARS-CoV-2 coronavirus). In certain embodiments, the antibodies and antigen-binding fragments disclosed herein can neutralize SARS-CoV-2 infection in in vitro infection models and/or animal infection models and/or in human subjects. Also provided are polynucleotides, vectors, host cells, and related compositions encoding antibodies and antigen-binding fragments, and the use of such antibodies, nucleic acids, vectors, host cells, and related compositions for treatment (e.g., reducing, delaying, eliminating or A method for preventing) SARS-CoV-2 infection in an individual and/or for the manufacture of a medicament for treating SARS-CoV-2 infection in an individual.

Before describing the present disclosure in greater detail, an understanding may be helpful to provide definitions of certain terms to be used herein. Other definitions are set forth throughout this disclosure.

As used herein, "SARS-CoV-2", also referred to herein as "Wuhan Seafood Market Pneumonia Virus" or "Wuhan Coronavirus" or "Wuhan CoV" or "novel CoV" or "nCoV" or "2019 nCoV" ” or “Wuhan nCoV”, a betacoronavirus believed to have lineage B (Sabe coronavirus). In late 2019, SARS-CoV-2 was first identified in Wuhan, Hubei Province, China, and by early 2020, spread within China and the rest of the world. Symptoms of SARS-CoV-2 infection include fever, dry cough and difficulty breathing.

The genome sequence of the SARS-CoV-2 isolate Wuhan-Hu-1 is provided in SEQ ID NO.: 1 (see also GenBank MN908947.3, January 23, 2020), and the amino acid translation of the genome provides In SEQ ID NO.: 2 (see also GenBank QHD43416.1, January 23, 2020). Like other coronaviruses (eg, SARS-CoV-1), SARS-CoV-2 contains a "spike" or surface ("S") type I transmembrane glycoprotein containing a receptor binding domain (RBD). It is believed that RBD mediates entry of lineage B SARS coronavirus into respiratory epithelial cells by binding to the cell surface receptor angiotensin-converting enzyme 2 (ACE2). Specifically, it is believed that the receptor binding motif (RBM) in the viral RBD interacts with ACE2.

The amino acid sequence of Wuhan-Hu-1 surface glycoprotein is provided in SEQ ID NO.:3. The amino acid sequence of Wuhan-Hu-1 RBD is provided in SEQ ID NO.:4. The S protein of SARS-CoV-2 shares approximately 73% amino acid sequence identity with SARS-CoV-1. The amino acid sequence of Wuhan-Hu-1 RBM is provided in SEQ ID NO.:5. Wuhan-Hu-1 RBD shares about 75% to 77% amino acid sequence similarity with SARS-CoV-1 RBD, and Wuhan-Hu-1 RBM shares about 50% amino acid sequence similarity with SARS-CoV-1 RBM sex.

Unless otherwise specified herein, SARS-CoV-2 Wuhan Hu-1 refers to comprising any of SEQ ID NO.: 2, 3 and 4, optionally having the gene body sequence set forth in SEQ ID NO.: 1 One or more of the amino acid sequences set forth in the virus.

Multiple emerging SARS-CoV-2 variants have emerged. Some SARS-CoV-2 variants contain the N439K mutation that enhances binding affinity to the human ACE2 receptor (Thomson, EC et al., The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity. bioRxiv , 2020). Some SARS-CoV-2 variants contain the N501Y mutation associated with increased transmissibility, including lineage B.1.1.7 found in the UK and South Africa, respectively (also known as 20I/501Y.V1 and VOC 202012/01; (del69 -70, del144, N501Y, A570D, D614G, P681H, T716I, S982A and D1118H mutations)) and B.1.351 (also known as 20H/501Y.V2; L18F, D80A, D215G, R246I, K417N, E484K, N501Y, D614G and A701V mutation) (Tegally, H., et al., Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv, 2020: p. 2020.12.21.20248640; Leung, K., et al., Early empirical assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020. medRxiv, 2020: p. 2020.12.20.20248581). B.1.351 also includes two other mutations K417N and E484K in the RBD domain of the SARS-CoV2 spike protein (Tegally, H. et al., Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS- CoV-2) lineage with multiple spike mutations in South Africa. medRxiv, 2020: p. 2020.12.21.20248640). Other SARS-CoV-2 variants include lineage B.1.1.28, which was first reported in Brazil; variant P.1, lineage B.1.1.28 (also known as 20J/501Y.V3), which was first reported in Japan Variant L452R, which was first reported in California, USA (Pan American Health Organization, Epidemiological update: Occurrence of variants of SARS-CoV-2 in the Americas, January 20, 2021, available at reliefweb.int/sites/reliefweb. int/files/resources/2021-jan-20-phe-epi-update-SARS-CoV-2.pdf). Other SARS-CoV-2 variants include SARS CoV-2 of clade 19A; SARS CoV-2 of clade 19B; SARS CoV-2 of clade 20A; SARS CoV-2 of clade 20B; SARS CoV-2 of clade 20C; SARS CoV-2 of clade 20D; SARS CoV-2 of clade 20E (EU1); SARS CoV-2 of clade 20F; CoV-2 of clade 20G ; SARS CoV-2 B1.1.207; and Rambaut, A. et al., A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Other SARS CoVs described in Nat Microbiol 5, 1403-1407 (2020) -2 Pedigree. The aforementioned SARS-CoV-2 variants and their amino acid and nucleotide sequences are incorporated herein by reference. Therefore, it should be understood that SARS-CoV-2 includes Wuhan Hu-1 and its variants, including the variants disclosed in the present invention.

In this specification, unless otherwise indicated, any concentration range, percentage range, ratio range or integer range should be understood to include any integer value within the recited range and, where appropriate, a fraction thereof (such as tenths of an integer) one and one percent). Furthermore, unless otherwise indicated, any numerical range described herein in relation to any physical characteristic such as a polymer subunit, size, or thickness is understood to include any integer within the range. As used herein, unless otherwise indicated, the term "about" means ±20% of the specified range, value or structure. It is to be understood that the term "a/an" as used herein refers to "one or more" of the listed components. It should be understood that the use of an alternative (eg, "or") means one of the alternatives, both, or any combination thereof. As used herein, the terms "including", "having" and "comprising" are used synonymously, and these terms and variations thereof are intended to be construed as non-limiting.

"Optional" or "optionally" means that a subsequently described element, component, event or circumstance may or may not occur, and that the description includes instances in which such element, component, event or circumstance occurs and in which it does not occur situation that occurred.

Additionally, it should be understood that individual constructs or groups of constructs derived from the various combinations of structures and subunits described herein are disclosed by this application to the same extent as if each construct or group of constructs were individually described. Accordingly, the selection of specific structures or specific subunits is within the scope of this disclosure.

The term "consisting essentially of" is different from "comprising," and refers to the specified substance or step claimed, or a substance or step that does not materially affect the essential characteristics of the claimed subject matter. For example, when the amino acid sequence of a protein domain, region, module, or protein includes extensions, deletions, mutations, or combinations thereof (eg, amino acids at the amino or carboxyl termini or between domains), A domain, region, or module (e.g., a binding domain) or protein "consists essentially of a specific amino acid sequence" which in combination occupies up to 20% (e.g., up to 15%, 10%, 8%, 6%, 5%, 4%, 3%, 2%, or 1%) and do not substantially affect (that is, the activity is reduced by no more than 50%, such as by no more than 40%, 30%, 25% %, 20%, 15%, 10%, 5% or 1%) domain, region, module or protein activity (eg, target binding affinity of the binding protein).

As used herein, "amino acid" refers to both naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code and those amino acids that are subsequently modified, such as hydroxyproline, gamma-carboxyglutamic acid, and O-phosphoserine. Amino acid analogs refer to compounds that have the same basic chemical structure as naturally occurring amino acids (i.e. α-carbon combined with hydrogen, carboxyl, amine and R groups), such as homoserine, norleucine acid, methionine, methionine, methyl methionine. These analogs have modified R groups (eg, n-leucine) or modified peptide backbones, yet retain the same basic chemical structure as a naturally occurring amino acid. An amino acid mimetic refers to a compound that has a structure that differs from the general chemical structure of an amino acid, but functions in a manner similar to that of a naturally occurring amino acid.

As used herein, "mutation" refers to a change in the sequence of a nucleic acid molecule or polypeptide molecule compared to a reference or wild-type nucleic acid molecule or polypeptide molecule, respectively. Mutations can cause several different types of sequence changes, including nucleotide or amino acid substitutions, insertions, or deletions.

"Conservative substitution" refers to amino acid substitutions that do not significantly affect or alter the binding characteristics of a particular protein. Typically, a conservative substitution is one in which a substituted amino acid residue is replaced by an amino acid residue with a similar side chain. Conserved substitutions include substitutions found in one of the following groups: Group 1; Alanine (Ala or A), Glycine (Gly or G), Serine (Ser or S), Threonine (Thr or T); group 2: aspartic acid (Asp or D), glutamic acid (Glu or Z); group 3: asparagine (Asn or N), glutamine (Gln or Q); Group 4: Arginine (Arg or R), Lysine (Lys or K), Histidine (His or H); Group 5: Isoleucine (Ile or I), Leucine (Leu or L), Methionine (Met or M), Valine (Val or V); and Group 6: Phenylalanine (Phe or F), Tyrosine (Tyr or Y), Tryptophan (Trp or W). Additionally or alternatively, amino acids can be grouped into conserved substitution groups by similar function, chemical structure, or composition (eg, acidic, basic, aliphatic, aromatic, or sulfur-containing). For example, an aliphatic grouping may include Gly, Ala, Val, Leu, and Ile for substitution purposes. Other conservative substitution groups include: Sulfur-containing: Met and cysteine (Cys or C); Acidic: Asp, Glu, Asn and Gln; Small aliphatic, non-polar or slightly polar residues: Ala, Ser, Thr, Pro and Gly; polar, negatively charged residues and their amides: Asp, Asn, Glu and Gln; polar, positively charged residues: His, Arg and Lys; large aliphatic, nonpolar residues: Met, Leu, Ile , Val and Cys; and large aromatic residues: Phe, Tyr and Trp. Additional information can be found in Creighton (1984) Proteins, W.H. Freeman and Company.

As used herein, "protein" or "polypeptide" refers to a polymer of amino acid residues. Proteins are suitable for naturally occurring amino acid polymers, as well as amino acid polymers suitable for use in which one or more amino acid residues are artificial chemical mimetics of the corresponding naturally occurring amino acids, and non-naturally occurring amino acid polymers. Amino acid polymers. Variants of the proteins, peptides and polypeptides of the present disclosure are also encompassed. In certain embodiments, variant proteins, peptides and polypeptides comprise or consist of at least 70%, 75%, 80%, 85%, 90% of the amino acid sequence of a defined or reference amino acid sequence described herein , 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.9% identical amino acid sequence composition.

A "nucleic acid molecule" or "polynucleotide" or "polynucleic acid" refers to a covalently linked subunit consisting of natural subunits (eg, purine or pyrimidine bases) or non-natural subunits (eg, pyridine rings) nucleotide polymer compounds. Purine bases include adenine, guanine, hypoxanthine, and xanthine, and pyrimidine bases include uracil, thymine, and cytosine. Nucleic acid molecules include polyribonucleic acid (RNA), which includes mRNA, microRNA, siRNA, viral genome RNA, and synthetic RNA; and polydeoxyribonucleotides (DNA), which includes cDNA, genome DNA, and synthetic DNA; wherein Either one can be single or double. If single-stranded, the nucleic acid molecule can be a coding strand or a non-coding (antisense) strand. Nucleic acid molecules encoding amino acid sequences include all nucleotide sequences encoding the same amino acid sequence. Some versions of nucleotide sequences may also include introns, to the extent that introns are removed by co-transcriptional or post-transcriptional mechanisms. In other words, different nucleotide sequences can encode the same amino acid sequence due to redundancy or simplicity of the genetic code or by splicing.

Variants of the nucleic acid molecules of the present disclosure are also encompassed. A variant nucleic acid molecule is at least 70%, 75%, 80%, 85%, 90%, and preferably 95%, 96%, 97%, 98%, of a nucleic acid molecule of a defined or reference polynucleotide described herein %, 99% or 99.9% identical, or 0.015M sodium chloride, 0.0015M sodium citrate at about 65-68°C or 0.015M sodium chloride, 0.0015M sodium citrate and 50% carboxylate at about 42°C Hybridizes to polynucleotides under stringent hybridization conditions of amide. Nucleic acid molecule variants retain the ability to encode their binding domains having the functionalities described herein, such as the ability to bind target molecules.

"Percent sequence identity" refers to the relationship between two or more sequences as determined by comparing the sequences. Preferred methods for determining sequence identity are designed to give the greatest match between the sequences being compared. For example, sequences are aligned for optimal comparison purposes (eg, a spacer can be introduced in one or both of the first and second amino acid or nucleic acid sequences for optimal alignment). In addition, non-homologous sequences can be ignored for comparison purposes. Unless otherwise indicated, the percent sequence identity referred to herein is calculated based on the length of the reference sequence. Methods for determining sequence identity and similarity can be found in publicly available computer programs. Sequence alignments and percent identity calculations can be performed using BLAST programs (eg, BLAST 2.0, BLASTP, BLASTN, or BLASTX). Mathematical algorithms used in the BLAST program can be found in Altschul et al., Nucleic Acids Res. 25:3389-3402, 1997. Within the context of this disclosure, it will be understood that when sequence analysis software is used for analysis, the analysis results are based on "defaults" of the referenced program. "Default" means any value or parameter set initially loaded by the software on first initialization.

The term "isolated" means that the material is removed from its original environment (eg, the natural environment if it is naturally occurring). For example, a naturally-occurring nucleic acid or polypeptide present in a living animal is not isolated, but the same nucleic acid or polypeptide is isolated from some or all coexisting materials in the natural system. Such nucleic acid may be part of a vector and/or such nucleic acid or polypeptide may be part of a composition (eg, cell lysate) and still be isolated because such vector or composition is not part of the nucleic acid or polypeptide's natural environment. part.

The term "gene" means a DNA or RNA segment involved in producing a polypeptide chain; in some cases, it includes regions preceding and following the coding region (eg, the 5' untranslated region (UTR) and the 3' UTR), and Intervening sequences (introns) between individual coding segments (exons).

"Functional variant" refers to a parent or reference compound that is structurally or substantially structurally similar to the disclosure, but differs in composition (eg, a base, atom, or functional group is different, added or removed) Polypeptides or polynucleotides that differ slightly in aspect such that the polypeptide or encoded polypeptide is capable of at least 50% efficiency, preferably at least 55%, 60%, 70%, 75%, 80%, 85%, of the activity of the parent polypeptide %, 90%, 95%, 96%, 97%, 98%, 99%, 99.9% or 100% level, perform at least one function of the parent polypeptide. In other words, when a functional variant is compared to a parent or reference polypeptide in a selected assay, such as an assay used to measure binding affinity (eg, Biacore® or tetramers that measure association (Ka) or dissociation (K _D ) constants A polypeptide of the present disclosure or a functional variant of an encoded polypeptide has "similar binding", "similar affinity" or "similar activity" when it exhibits no more than 50% reduction in potency.

As used herein, a "functional portion" or "functional fragment" refers to a polypeptide or polynucleotide comprising only the domain, portion, or fragment of the parent or reference compound, and the polypeptide or encoded polypeptide retains the domain, portion, or fragment of the parent or reference compound. At least 50% of the activity relative to the part or fragment, preferably at least 55%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, of the activity of the parent polypeptide, 98%, 99%, 99.9% or 100% level, or provide biological benefit (eg, effector function). When the functional portion or fragment exhibits no more than a 50% reduction in potency compared to the parent or reference polypeptide (with respect to affinity, preferably no more than 20% or 10% compared to the parent or reference, or no more than a log difference), the present A "functional portion" or "functional fragment" of a polypeptide or encoded polypeptide of the disclosure has "similar binding" or "similar activity."

As used herein, the terms "engineered", "recombinant" or "non-natural" refer to an organism, microorganism, cell, Nucleic acid molecules or vectors in which such changes or modifications are introduced by genetic engineering (ie, human intervention). Genetic alterations include modifications such as the introduction of expressible nucleic acid molecules encoding functional RNAs, proteins, fusion proteins or enzymes, or additions, deletions, substitutions of other nucleic acid molecules, or other functional disruption of the genetic material of a cell. Additional modifications include, for example, non-coding regulatory regions, wherein the modification alters the expression of the polynucleotide, gene or operon.

As used herein, "heterologous" or "non-endogenous" or "exogenous" refers to any gene, protein, compound, nucleic acid molecule or activity that is not native to the host cell or individual, or that has been altered by the host cell Or any gene, protein, compound, nucleic acid molecule or activity native to the individual. Heterologous, non-endogenous, or exogenous includes genes, proteins, compounds, or nucleic acid molecules that have been mutated or otherwise altered such that structure, activity, or both differ between the native and altered genes, proteins, compounds, or nucleic acid molecules. Nucleic acid molecules. In certain embodiments, a heterologous, non-endogenous, or exogenous gene, protein, or nucleic acid molecule (eg, receptor, ligand, etc.) may not be endogenous to the host cell or individual, but the actual Above, nucleic acids encoding such genes, proteins or nucleic acid molecules can be added to a host cell by conjugation, transformation, transfection, electroporation or the like, wherein the added nucleic acid molecule can be integrated into the host cell genome or It may exist in the form of extrachromosomal genetic material (eg, as a plastid or other self-replicating vector). The term "homology" or "homolog" refers to a gene, protein, compound, nucleic acid molecule or activity found in or derived from a host cell, species or strain. For example, a heterologous or exogenous polynucleotide or gene encoding a polypeptide can be homologous to the native polynucleotide or gene and encode a homologous polypeptide or activity, but the polynucleotide or polypeptide can be With altered structure, sequence, level of expression, or any combination thereof. The non-endogenous polynucleotide or gene and the encoded polypeptide or activity can be from the same species, different species, or a combination thereof.

In certain embodiments, a nucleic acid molecule or portion thereof native to the host cell will be considered heterologous to the host cell if it has been altered or mutated, or if it has heterologous expression control sequences altered or has generally not been associated with A nucleic acid molecule native to the host cell may be considered to be heterologous by altering the endogenous expression control sequences associated with the nucleic acid molecule native to the host cell. Additionally, the term "heterologous" can refer to a biological activity that is different, altered, or not endogenous to the host cell. As described herein, more than one heterologous nucleic acid molecule can be introduced into a host cell as a single nucleic acid molecule, as multiple individually controlled genes, as a polycistronic nucleic acid molecule, as a single nucleic acid molecule encoding a fusion protein, or any combination thereof .

As used herein, the term "endogenous" or "native" refers to a polynucleotide, gene, protein, compound, molecule or activity that is normally present in a host cell or individual.

The term "expression" as used herein refers to a method of producing a polypeptide based on the coding sequence of a nucleic acid molecule, such as a gene. The method can include transcription, post-transcriptional control, post-transcriptional modification, translation, post-translational control, post-translational modification, or any combination thereof. The expressed nucleic acid molecule is typically operably linked to an expression control sequence (eg, a promoter).

The term "operably linked" refers to the association of two or more nucleic acid molecules on a single nucleic acid fragment such that the function of one is affected by the other. For example, a promoter is operably linked to a coding sequence (ie, the coding sequence is under the transcriptional control of the promoter) when the promoter is capable of affecting the performance of the coding sequence. "Disconnected" means that the related genetic elements are not closely related to each other and that the function of one does not affect the other.

As described herein, more than one heterologous nucleic acid molecule can be used as a single nucleic acid molecule, as multiple individually controlled genes, as a polycistronic nucleic acid molecule, as a single nucleic acid molecule encoding a fusion protein (eg, the heavy chain of an antibody), or Any combination thereof is introduced into the host cell. When two or more heterologous nucleic acid molecules are introduced into a host cell, it is understood that the two or more heterologous nucleic acid molecules can be introduced as a single nucleic acid molecule on separate vectors (eg, on a single vector) , integrated into the host chromosome at a single site or multiple sites, or any combination thereof. References to the number of heterologous nucleic acid molecules or protein activities refer to the number of encoding nucleic acid molecules or protein activities, not the number of individual nucleic acid molecules introduced into the host cell.

The term "construct" refers to any polynucleotide comprising a recombinant nucleic acid molecule (or, when the context clearly dictates, a fusion protein of the present disclosure). The (polynucleotide) construct can be present in a vector (eg, bacterial vector, viral vector), or can be integrated into a gene body. A "vector" is a nucleic acid molecule capable of transporting another nucleic acid molecule. A vector can be, for example, a plastid, a cosmid, a virus, an RNA vector, or a linear or circular DNA or RNA molecule, which can include chromosomal, non-chromosomal, semi-synthetic or synthetic nucleic acid molecules. Vectors of the present disclosure also include translocation subsystems (eg, Sleeping Beauty, see eg, Geurts et al., Mol. Ther. 8:108, 2003: Mátés et al., Nat. Genet. 41:753, 2009). Exemplary vectors are those capable of autonomous replication (episomal vectors), capable of delivering polynucleotides to cellular genomes (eg, viral vectors), or capable of expressing the nucleic acid molecules to which they are linked (expression vectors).

As used herein, "expression vector" or "vector" refers to a DNA construct containing a nucleic acid molecule operably linked to suitable control sequences that enable expression of the nucleic acid molecule in a suitable host. Such control sequences include promoters to effect transcription, optional operator sequences to control such transcription, sequences encoding suitable mRNA ribosomal binding sites, and sequences to control the termination of transcription and translation. The vector can be a plastid, a phage particle, a virus, or only a potential gene body insertion. Once transformed into a suitable host, the vector can replicate and function independently of the host genome, or can in some cases integrate into the genome itself, or deliver the polynucleotides contained in the vector to those without the vector sequence in the genome. In the present specification, "plastid", "expression plasmid", "virus" and "vector" are often used interchangeably.

In the context of inserting a nucleic acid molecule into a cell, the term "introduced" means "transfection", "transformation" or "transduction" and includes references to the incorporation of a nucleic acid molecule into a eukaryotic or prokaryotic cell, Wherein the nucleic acid molecule can be incorporated into the genome of the cell (eg, chromosomal, plastid, chromosomal or mitochondrial DNA), converted into an autonomous replicon or transiently expressed (eg, infected mRNA).

In certain embodiments, the polynucleotides of the present disclosure may be operably linked to an element of a vector. For example, the polynucleotide sequences necessary to effect performance and processing of the joined coding sequences can be operably linked. Expression control sequences may include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals, such as splicing and polyadenylation signals; sequences to stabilize cytoplasmic mRNA; Kozak consensus sequence); sequences that enhance protein stability; and possible sequences that enhance protein secretion. An expression control sequence can be operably linked if it is contiguous with the gene of interest and an expression control sequence that acts in trans or at a distance to control the gene of interest.

In certain embodiments, the vector comprises a plastid vector or a viral vector (eg, a lentiviral vector or a gamma-retroviral vector). Viral vectors include retroviruses; adenoviruses; small viruses (eg, adeno-associated viruses); coronaviruses; , Paramyxoviruses (eg, measles and Sendai); positive-stranded RNA viruses, such as picornaviruses and alphaviruses; and double-stranded DNA viruses, including adenoviruses, herpesviruses (eg, herpes simplex types 1 and 2, Epstein-Barr virus Epstein-Barr virus, cytomegalovirus) and poxviruses (eg vaccinia, fowlpox and canarypox). Other viruses include, for example, Norwalk virus, tocovirus, flavivirus, reovirus, papovavirus, hepadnavirus, and hepatitis virus. Examples of retroviruses include: avian leukemic sarcoma virus, mammalian type C virus, type B virus, type D virus, HTLV-BLV group, lentivirus, foamy virus (Coffin, J. M., Retroviridae: The viruses and their replication , Fundamental Virology, 3rd ed., B.N. Fields et al. eds., Lippincott-Raven Publishers, Philadelphia, 1996).

A "retrovirus" is a virus that has an RNA genome that is reverse transcribed into DNA using reverse transcriptase, which subsequently incorporates the reverse transcribed DNA into the host cell genome. "GammaRetrovirus" means a genus of the Retroviridae family. Examples of gamma retroviruses include mouse stem cell virus, murine leukemia virus, feline leukemia virus, feline sarcoma virus, and avian reticuloendothelial proliferation virus.

"Lentiviral vectors" include HIV-like lentiviral vectors for gene delivery, which can be integrated or unintegrated, have relatively large encapsulation capabilities, and can transduce a range of different cell types. Lentiviral vectors are typically produced following transient transfection of three (encapsulation, envelope and transfer) or more plastids into producer cells. Like HIV, lentiviral vectors enter target cells through the interaction of viral surface glycoproteins with receptors on the cell surface. After entry, viral RNA is reverse transcribed, which is mediated by the viral reverse transcriptase complex. The product of reverse transcription is double-stranded linear viral DNA, which is the substrate for the virus that integrates into the DNA of infected cells.

In certain embodiments, the viral vector may be a gamma retrovirus, such as a Moloney murine leukemia virus (MLV) derived vector. In other embodiments, the viral vector can be a more complex retrovirus-derived vector, such as a lentivirus-derived vector. HIV-1 derived vectors fall into this category. Other examples include lentiviral vectors derived from HIV-2, FIV, Equine Infectious Anemia Virus, SIV, and Maedi-Visna virus (sheep lentivirus). Methods of using retroviral and lentiviral viral vectors and encapsulating cells for transduction of mammalian host cells with virions containing transgenic genes are known in the art and have been previously described, for example, in US Pat. No. 8,119,772 No.; Walchli et al, PLoS One 6:327930, 2011; Zhao et al, J. Immunol. 174:4415, 2005; Engels et al, Hum. Gene Ther. 14:1155, 2003; Frecha et al, Mol. Ther 18:1748, 2010; and Verhoeyen et al., Methods Mol. Biol. 506:97, 2009. Retroviral and lentiviral vector constructs and expression systems are also commercially available. Other viral vectors may also be used for polynucleotide delivery including DNA viral vectors, including, for example, adenovirus-based vectors and adeno-associated virus (AAV)-based vectors; vectors derived from herpes simplex virus (HSV), including Amplicon vectors, replication deficient HSV and attenuated HSV (Krisky et al., Gene Ther. 5:1517, 1998).

Other vectors that can be used in the compositions and methods of the present disclosure include vectors derived from baculoviruses and alpha-viruses. (Jolly, D J. 1999. Emerging Viral Vectors. pp. 209-40 in Friedmann T. ed. The Development of Human Gene Therapy. New York: Cold Spring Harbor Lab), or plastid vectors (such as Sleeping Beauty or other transgenic seat carrier).

When the viral vector genome contains multiple polynucleotides to be expressed in the host cell as separate transcripts, the viral vector may also contain dicistronic or polynucleotides between the two (or more) transcripts. Additional sequences expressed by cistrons. Examples of such sequences for use in viral vectors include the internal ribosome entry site (IRES), the Flynn cleavage site, the viral 2A peptide, or any combination thereof.

Further described herein are plastid vectors, including plastid vectors encoding DNA-based antibodies or antigen-binding fragments, for direct administration to an individual.

As used herein, the term "host" refers to a cell or microorganism targeted for genetic modification with a heterologous nucleic acid molecule to produce a polypeptide of interest (eg, an antibody of the present disclosure).

A host cell can include an acceptable vector or any individual cell or cell culture that incorporates a nucleic acid or expresses a protein. The term also encompasses host cell progeny, whether genetically or phenotypically identical or different. Suitable host cells may depend on the vector, and may include mammalian cells, animal cells, human cells, simian cells, insect cells, yeast cells, and bacterial cells. These cells can be induced to incorporate vectors or other substances by using viral vectors, transformation via calcium phosphate precipitation, DEAE-polydextrose, electroporation, microinjection, or other methods. See, eg, Sambrook et al., Molecular Cloning: A Laboratory Manual 2d ed. (Cold Spring Harbor Laboratory, 1989).

In the context of SARS-CoV-2 infection, "host" refers to a cell or individual infected with SARS-CoV-2.

As used herein, "antigen" or "Ag" refers to an immunogenic molecule that elicits an immune response. This immune response may involve antibody production, activation of specific immunologically competent cells, complement activation, antibody-dependent cytotoxicity, or any combination thereof. Antigens (immunogenic molecules) can be, for example, peptides, glycopeptides, polypeptides, glycopolypeptides, polynucleotides, polysaccharides, lipids, or analogs thereof. It is readily apparent that antigens can be synthesized, recombinantly produced, or derived from biological samples. Exemplary biological samples that may contain one or more antigens include tissue samples, stool samples, cells, biological fluids, or combinations thereof. Antigens can be produced by cells that have been modified or genetically engineered to express the antigen. Antigens can also be present in SARS-CoV-2 (eg, surface glycoproteins or portions thereof), such as in virions, or expressed or presented on the surface of cells infected by SARS-CoV-2.

The term "epitope" or "epitope" includes any molecule, structure, amino acid sequence or protein determinant that is recognized and specifically bound by a cognate binding molecule such as an immunoglobulin or other binding molecule, domain or protein. Epitopic determinants typically contain chemically active surface groups of molecules, such as amino acids or sugar side chains, and can have specific three-dimensional structural properties as well as charge-to-mass ratio properties. When the antigen is or comprises a peptide or protein, the epitope may include contiguous amino acids (eg, linear epitopes), or may include amino acids from different parts or regions of the protein that are brought into proximity by protein folding (eg, non-linear epitopes) contiguous or conformational epitopes), or closely adjacent non-contiguous amino acids that are not involved in protein folding. Antibodies, antigen-binding fragments and compositions

In one aspect, the present disclosure provides an isolated antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL) and capable of binding to the surface of SARS-CoV-2 A glycoprotein, the heavy chain variable domain (VH) comprises CDRH1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3. In certain embodiments, the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on the cell surface of a host cell and/or on a SARS-CoV-2 virion.

In certain embodiments, an antibody or antigen-binding fragment of the present disclosure binds or associates with a SARS-CoV-2 surface glycoprotein epitope or an antigen comprising the epitope, but not with any other molecule or component in the sample Significantly combined or combined.

In certain embodiments, an antibody or antigen-binding fragment of the present disclosure binds or associates (eg, binds) to a SARS-CoV-2 surface glycoprotein epitope, and may also bind to a source from another coronavirus present in the sample An epitope (eg, SARS-CoV-1) binds or associates, but does not significantly bind or associate with any other molecule or component in the sample. In other words, in certain embodiments, the antibodies or antigen-binding fragments of the present disclosure cross-react with SARS-CoV-2 and one or more additional coronaviruses.

In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure specifically bind to SARS-CoV-2 surface glycoproteins. As used herein, "specific binding" refers to the association or association of an antibody or antigen-binding fragment with an antigen with an affinity or Ka (ie, the equilibrium binding constant for _a specific binding interaction, in units of 1/M) equal to or greater than 10 ⁵ M ^-1 (which is equal to the ratio of the association rate [ _Kon ] to the dissociation rate [ _Koff ] for this association reaction, but not significantly associated or associated with any other molecule or component in the sample. Alternatively, affinity can be defined as the equilibrium dissociation constant (K _D ) for a particular binding interaction in M (eg, 10 ^-5 M to 10 ^-13 M). Antibodies can be classified as "high affinity" antibodies or "low affinity" antibodies. "High affinity" antibodies refer to _Kas of at least 10 ⁷ M ^-1 , at least 10 ⁸ M ^-1 , at least 10 ⁹ M ^-1 , at least 10 ¹⁰ M ^-1 , at least 10 ¹¹ M ^-1 , at least 10 ¹² M ^{- 1} or at least 10 ¹³ M ^-1 of those antibodies. "Low affinity" antibodies refer to those antibodies whose ^Ka is at most ₁₀₇ M" ¹ , at most ¹⁰⁶ M" ¹ , at most ¹⁰⁵ M" ¹ . Alternatively, affinity can be defined as the equilibrium dissociation constant (K _D ) for a particular binding interaction in M (eg, 10 ^-5 M to 10 ^-13 M).

Various assays are known for identifying antibodies of the present disclosure that bind specific targets and determining binding domain or binding protein affinity, such as Western blot, ELISA (eg, direct, indirect, or sandwich), analytical ultracentrifugation, spectroscopy, and Surface Plasmon Resonance (Biacore®) analysis (see e.g., Scatchard et al, Ann. N.Y. Acad. Sci. 51:660, 1949; Wilson, Science 295:2103, 2002; Wolff et al, Cancer Res. 53:2560 , 1993; and US Pat. Nos. 5,283,173, 5,468,614 or equivalent). Assays for assessing affinity or apparent or relative affinity are known.

In certain instances, binding can be achieved by recombinantly expressing the SARS-CoV-2 antigen in host cells (eg, by transfection) and using antibody pairs (eg, immobilized, or immobilized and pre-infiltrated) Host cell immunostaining, and determination of binding by flow cytometry (eg, using a ZE5 cell analyzer (BioRad®) and FlowJo software (TreeStar) for binding. In some embodiments, positive binding can be determined by the expression of SARS-CoV-2 Cells are defined by differential staining of the antibody relative to control (eg, mock) cells.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure bind to the SARS-CoV-2 S protein, as measured using biolayer interferometry.

In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure bind to the SARS-CoV-2 _S protein, wherein the KD is less than about ^4.5x10 "9M, less than about 5x10" ^9M , less than about 1x10 ^-10 M, less than about ^5x10-10 M, less than about ^1x10-11 M, less than about ^5x10-11 M, less than about ^1x10-12 M, or less than about ^5x10-12 M. In some embodiments, the antibodies or antigen-binding fragments of the present disclosure bind to the SARS-CoV-2 _S protein RBD, wherein the KD is less than about ^4.5x10 "9M, less than about 5x10" ^9M , less than about 1x10 ^-10 M, less than about ^5x10-10 M, less than about ^1x10-11 M, less than about ^5x10-11 M, less than about ^1x10-12 M, or less than about ^5x10-12 M.

Certain characteristics of the disclosed antibodies or antigen-binding fragments can be described using IC50 or EC50 values. In certain embodiments, the IC50 is the concentration of a composition (eg, an antibody) that causes a half-maximal inhibition of the indicated biological or biochemical function, activity, or response. In certain embodiments, the EC50 is the concentration of a constituent that provides a half-maximal response in an assay. In some embodiments, IC50 and EC50 are used interchangeably, eg, to describe the ability of the disclosed antibodies or antigen-binding fragments to neutralize infection by SARS-CoV-2.

In certain embodiments, the antibodies of the present disclosure are capable of neutralizing infection caused by SARS-CoV-2. As used herein, a "neutralizing antibody" is one that neutralizes, ie, prevents, inhibits, reduces, hinders or interferes with the ability of a pathogen to initiate and/or maintain infection in a host. The terms "neutralizing antibody" and "antibody for neutralizing" or "antibody for neutralizing" are used interchangeably herein. In any of the embodiments disclosed herein, the antibody or antigen-binding fragment is capable of preventing and/or neutralizing in vitro infection models and/or in vivo animal infection models (eg, using Syrian hamster model for intranasal delivery) and/or SARS-CoV-2 infection in humans.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of neutralizing SARS-CoV-2 infection with an IC50 of about 16 to about 20 μg/ml or by pseudo-patterning via the SARS-CoV-2 S protein virus infection. In some embodiments, the antibody or antigen-binding fragment is capable of neutralizing SARS-CoV-2 infected or pseudopatterned virus with the SARS-CoV-2 S protein with an IC50 of about 3 to about 4 μg/ml. In any of the embodiments disclosed herein, the antibody or antigen-binding fragment is capable of neutralizing SARS-CoV-2 infection or SARS-CoV-2 infection with IC50, IC80 and/or IC90 as shown in Table 4 2 S-protein pseudo-patterned virus.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure, or compositions comprising two or more antibodies or antigen-binding fragments, are capable of neutralizing SARS-CoV-2 with an IC50 of about 0.8 to about 0.9 μg/ml infection, or a virus pseudopatterned with the SARS-CoV-2 S protein. In some embodiments, the antibodies or antigen-binding fragments of the present disclosure, or compositions comprising two or more antibodies or antigen-binding fragments, are capable of neutralizing SARS-CoV-2 with an IC50 of about 0.5 to about 0.6 μg/ml infection, or a virus pseudopatterned with the SARS-CoV-2 S protein. In some embodiments, the antibodies or antigen-binding fragments of the present disclosure, or compositions comprising two or more antibodies or antigen-binding fragments, are capable of neutralizing SARS-CoV-2 with an IC50 of about 0.1 to about 0.2 μg/ml infection, or a virus pseudopatterned by SARS-CoV-2.

In certain embodiments, the antibody or antigen-binding fragment (i) recognizes an epitope in the ACE2 receptor binding motif (RBM, SEQ ID NO.: 5) of SARS-CoV-2; (ii) is capable of blocking SARS-CoV-2 - Interaction between CoV-2 and human ACE2 (i.e. partial or complete blocking of the interaction via binding to SARS-CoV-2); (ii) capable of binding to SARS-CoV-2 S protein; (iv) Identify epitopes conserved in the ACE2 RBM of SARS-CoV-2 and in the ACE2 RBM of SARS-CoV-1; (v) cross-react against SARS-CoV-2 and SARS-CoV-1; (vi) identify an epitope in the SARS-CoV-2 surface glycoprotein that is not in the ACE2 RBM; or (vii) any combination of (i)-(vii).

Unless explicitly defined herein, terms as understood by those skilled in the art of antibodies are each given the meaning obtained in the art. For example, the term "antibody" refers to an intact antibody that comprises at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds, and that has or remains bound to recognition by the intact antibody Any antigen-binding portion or fragment of an intact antibody, such as a scFv, Fab or Fab'2 fragment, that has the ability to target an antigenic molecule. Thus, the term "antibody" is used herein in the broadest sense and includes both polyclonal and monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments thereof, including antigen-binding fragment (Fab) fragments, F( ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rIgG) fragments, single-chain antibody fragments, including single-chain variable fragments (scFv), and single-domain antibody (eg sdAb, sdFv, Nanobody) fragments . The term encompasses genetically engineered and/or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and hetero-binding antibodies, multispecific antibodies (eg bispecific) antibodies, diabodies, tri- and tetrabodies, tandem di-scFvs, tandem tri-scFvs. Unless otherwise specified, the term "antibody" is understood to encompass functional antibody fragments thereof. The term also encompasses whole or full-length antibodies, including antibodies of any class or subclass, including IgG and its subclasses (IgGl, IgG2, IgG3, IgG4), IgM, IgE, IgA, and IgD.

The terms " _VL " or "VL" and " _VH " or "VH" refer to the variable binding regions from antibody light and antibody heavy chains, respectively. In certain embodiments, VL is of the kappa (κ) class (also "VK" herein). In certain embodiments, VL is of the lambda (λ) class. The variable binding regions comprise discrete well-defined subregions called "complementarity determining regions" (CDRs) and "framework regions" (FRs). The terms "complementarity determining regions" and "CDRs" are synonymous with "hypervariable regions" or "HVRs" and refer to amino acid sequences within the variable regions of an antibody that, in general, together confer antigen specificity and/or the antibody The binding affinity is where consecutive CDRs (ie, CDR1 and CDR2, CDR2 and CDR3) are separated from each other in the primary structure by framework regions. There are three CDRs in each variable region (HCDRl, HCDR2, HCDR3; LCDRl, LCDR2, LCDR3; also known as CDRH and CDRL, respectively). In certain embodiments, the antibody VH comprises the following four FRs and three CDRs: FR1-HCDR1-FR2-HCDR2-FR3-HCDR3-FR4; and the antibody VL comprises the following four FRs and three CDRs: FR1-LCDR1- FR2-LCDR2-FR3-LCDR3-FR4. In general, VH and VL together form an antigen binding site via their corresponding CDRs.

As used herein, "variants" of CDRs refer to functional variants of CDR sequences with up to 1 to 3 amino acid substitutions (eg, conservative or non-conservative substitutions), deletions, or combinations thereof.

CDRs and framework regions can be numbered according to any known method or scheme, such as the Kabat, Chothia, EU, IMGT or AHo numbering scheme (see, e.g., Kabat et al., "Sequences of Proteins of Immunological Interest, US Dept. Health and Human" Services, Public Health Service National Institutes of Health, 1991, 5th ed.; ^Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)); Lefranc et al., Dev. Comp. Immunol. 27:55, 2003; Honegger and Plückthun, J. Mol. Bio. 309:657-670 (2001)). Equivalent residue positions can be used using the Antigen Receptor Numbering and Receptor Classification (ANARCI) software tool (2016, Bioinformatics 15:298- 300) annotate and compare different molecules. Thus, identifying CDRs of exemplary variable domain (VH or VL) sequences as provided herein according to one numbering scheme does not include antibodies comprising CDRs of the same variable domain determined using a different numbering scheme In certain embodiments, there is provided an antibody or antigen-binding fragment comprising CDRs according to the VH sequence of any one of the following: SEQ ID NO.: 22, 32, 42, 52, 62, 72, 74, 84, 96, 106, 119, 129, 139, 150, 163, 173, 175, 178, 186, 189, 191, 198, 208, 218, 228, 240, 254, 264, 274, 284, 298, 312, 322, 332, 350, 351, 353, 359, 361, 363, 365, 367, 368, 369, 379, 389, 399, 409, 419, 429, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 626, 628, 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 692, 740, 741, 742, 743, 748, 749, 750, 752, 754, 756, 758, 759, 761, 762 and 764 and the CDRs according to the VL sequence of any of the following: SEQ ID NO.: 26, 36, 46, 56, 66, 78, 88, 94, 100, 110, 123, 133, 143, 154, 157, 168, 194, 196, 202, 212, 222, 232, 238, 244, 250, 252, 258, 268, 278, 288, 294, 296, 302, 308, 310, 316 , 326, 336, 355, 357, 373, 383, 393, 403, 413, 423, 438, 448, 458, 468, 478, 488, 498, 508, 518, 528, 538, 548, 558, 568, 578 , 588, 598, 608, 618, 686, 696, 738, 744, and 746, as determined using any known CDR numbering method, including Kabat, Chothia, EU, IMGT, Martin (Enhanced Chothia), contact, and AHo numbering methods . In some embodiments, the CDRs are numbered according to the IMGT method. In certain embodiments, the CDRs are according to an antibody numbering method developed by the Chemical Computation Group (CCG); eg, using Molecular Operating Environment (MOE) software (www.chemcomp.com).

In certain embodiments, there is provided an antibody or an antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein: (i) the CDRH1 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NO.: 23 , 33, 43, 53, 63, 75, 85, 97, 107, 120, 130, 140, 147, 160, 170, 174, 183, 190, 199, 209, 219, 229, 241, 255, 265, 275 , 285, 299, 313, 323, 333, 370, 380, 390, 400, 410, 420, 430, 435, 445, 455, 465, 475, 485, 495, 505, 515, 525, 535, 545, 555 , 565, 575, 585, 595, 605, 615, 631, 693, 740, 741, 742 and 743, or sequence variants thereof comprising one, two or three acid substitutions, one or more of these substitutions is optionally a conservative substitution and/or is a substitution to a germline encoded amino acid; (ii) the CDRH2 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NO. : 24, 34, 44, 54, 64, 76, 86, 98, 108, 121, 131, 141, 148, 151, 161, 171, 184, 200, 210, 220, 230, 242, 256, 266, 276 , 286, 300, 314, 324, 334, 352, 360, 362, 364, 366, 371, 381, 391, 401, 411, 421, 431, 436, 446, 456, 466, 476, 486, 496, 506 , 516, 526, 536, 546, 556, 566, 576, 586, 596, 606, 616, 625, 632, 635, 637, 639, 641, 643, 645, 647, 649, 651, 653, 655, 657 , 659, 661, 663, 665, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685 and 694, or sequence variants thereof comprising one, two or three amino acid substitutions, One or more of these substitutions are optionally conservative substitutions and/or are substitutions for germline encoded amino acids; (iii) the CDRH3 comprises an amino acid sequence according to any of the following or It consists of: SEQ ID NO.: 25, 35, 45, 55, 65, 77, 87, 99, 109, 122, 132, 14 2, 149, 162, 164, 165, 172, 176, 177, 179, 180, 185, 187, 188, 201, 211, 221, 231, 243, 257, 267, 277, 287, 301, 315, 325, 335, 354, 372, 382, 392, 402, 412, 422, 432, 437, 447, 457, 467, 477, 487, 497, 507, 517, 527, 537, 547, 557, 567, 577, 587, 597, 607, 617, 627, 633, 695, 751, 753, 755, 757, 760, 763, 765 and 766, or sequence variants thereof comprising one, two or three amino acid substitutions, such substitutions One or more of these are optionally conservative substitutions and/or are substitutions for germline encoded amino acids; (iv) the CDRL1 comprises or consists of an amino acid sequence according to any of the following : SEQ ID NO.: 27, 37, 47, 57, 67, 79, 89, 101, 111, 124, 134, 144, 152, 155, 156, 158, 159, 166, 181, 192, 203, 213, 223, 233, 245, 259, 269, 279, 289, 303, 317, 327, 337, 356, 374, 384, 394, 404, 414, 424, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 687 and 697, or sequence variants thereof comprising one, two or three amino acid substitutions, such substitutions One or more of which are optionally conservative substitutions and/or are substitutions for germline encoded amino acids; (v) the CDRL2 comprises or consists of an amino acid sequence according to any of the following : SEQ ID NO.: 28, 38, 48, 58, 68, 80, 90, 102, 112, 125, 135, 145, 153, 167, 182, 193, 204, 214, 224, 234, 246, 260, 270, 280, 290, 304, 318, 328, 338, 375, 385, 395, 405, 415, 425, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 688 and 698, or sequence variants thereof comprising one, two or three amino acid substitutions, one or more of which are optionally Conservative substitutions and/or are substitutions for germline encoded amino acids; and/or (vi) the CDRL3 comprises according to the following The amino acid sequence of any one of or consisting of: SEQ ID NO.: 29, 39, 49, 59, 69, 81, 91, 103, 113, 126, 136, 146, 169, 195, 197, 205 , 215, 225, 235, 247, 261, 271, 281, 291, 305, 319, 329, 339, 358, 376, 386, 396, 406, 416, 426, 441, 451, 461, 471, 481, 491 , 501, 511, 521, 531, 541, 551, 561, 571, 581, 591, 601, 611, 621, 689, 699, 745 and 747, or those containing one, two or three amino acid substitutions Sequence variants, one or more of these substitutions are optionally conservative substitutions and/or substitutions for germline-encoded amino acids, wherein the antibody or antigen-binding fragment is capable of binding to a host cell-expressed Surface glycoprotein of SARS-CoV-2 on the cell surface.

In any of the embodiments disclosed herein, the antibody or antigen-binding fragment is capable of preventing and/or neutralizing SARS-CoV in an in vitro infection model and/or in an in vivo animal infection model and/or in humans CoV-2 infection.

In any of the embodiments disclosed herein, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences according to: (i) SEQ ID NO., respectively: 23-25 and 27-29; (ii) SEQ ID NO.: 33-35 and 37-39, respectively; (iii) SEQ ID NO.: 43-45 and 47-49, respectively; (iv) SEQ ID NO.: 43-45 and 47-49, respectively ID NO.: 53-55 and 57-59; (v) respectively SEQ ID NO.: 63-65 and 67-69; (vi) respectively SEQ ID NO.: 75-77 and 79-81; (vii) ) are respectively SEQ ID NO.: 85-87 and 89-91; (viii) are respectively SEQ ID NO.: 97-99 and 101-103; (ix) are respectively SEQ ID NO.: 107-109 and 111- 113; (x) are respectively SEQ ID NO.: 120-122 and 124-126; (xi) are respectively SEQ ID NO.: 130-132 and 134-136; (xii) are respectively SEQ ID NO.: 23 or any of 147, 24, 148 or 151, 25 or 149, any of 27, 152, 155, 156, 158 or 159, 28 or 153, and 29; (xiii) are SEQ ID NO. : 43 or 160, 44 or 161, any one of 45, 162, 164 or 165, 47 or 166, 48 or 167, and 49 or 169; (xiv) are respectively SEQ ID NO.: 130, 170 or 174 any one of, 130, 131, 132, 134 or 181, 135 or 182, and 136; (xv) are respectively any one of SEQ ID NO.: 53, 183 or 190, 54 or 184, 55, any one of 185, 187 or 188, any one of 57 or 192, 58 or 193, and any one of 59, 195 or 197; (xvi) are SEQ ID NO.: 199-201 and 203-205; (xvii) are respectively SEQ ID NO.: 209-211 and 213-215; (xviii) are respectively SEQ ID NO.: 219-221 and 223-225; (xix) are respectively SEQ ID NO.: 229-231 and 233-235; (xx) are SEQ ID NO.: 241-243 and 245-247 respectively; (xxi) are SEQ ID NO.: 255-257 and 259-261 respectively; (xxii) are SEQ ID NO.: 255-257 and 259-261 respectively ID N O.: 265-267 and 269-271; (xxiii) are respectively SEQ ID NO.: 275-277 and 279-281; (xxiv) are respectively SEQ ID NO.: 285-287 289-291, (xxv) are respectively are SEQ ID NO.: 299-301 and 303-305; (xxvi) are respectively SEQ ID NO.: 313-315 and 317-319; (xxvii) are respectively SEQ ID NO.: 323-325 and 327-329; (xxviii) are SEQ ID NO.: 333-335 and 337-339, respectively; (xxix) are SEQ ID NO.: 229, 230 or 352, 231 or 354, and 233 or 356, 234, and 235 or 358, respectively; (xxx) are any of SEQ ID NO.: 313, 314, 360, 362, 364 or 366, 315 and 317-319, respectively; (xxxi) are SEQ ID NO.: 370-372 and 374-376, respectively (xxxii) are respectively SEQ ID NO.: 380-382 and 384-386; (xxxiii) are respectively SEQ ID NO.: 390-392 and 394-396; (xxxiv) are respectively SEQ ID NO.: 400-402 and 404-406; (xxxv) are respectively SEQ ID NO.: 410-412 and 414-416; (xxxvi) are respectively SEQ ID NO.: 420-422 and 424-426; (xxxvii) are respectively SEQ ID NO. : 435-437 and 439-441; (xxxviii) are respectively SEQ ID NO.: 445-447 and 449-451; (xxxix) are respectively SEQ ID NO.: 455-457 and 459-461; (xxxx) are respectively SEQ ID NO.: 465-467 and 469-471; (xxxxi) are SEQ ID NO.: 475-477 and 479-481, respectively; (xxxxii) are SEQ ID NO.: 485-487 and 489-491, respectively; ( xxxxiii) are respectively SEQ ID NO.: 494-497 and 499-501; (xxxxiv) are respectively SEQ ID NO.: 505-507 and 509-511; (xxxxv) are respectively SEQ ID NO.: 515-517 and 519 -521; (xxxxvi) are respectively SEQ ID NO.: 525-527 and 529-531; (xxxxvii) are respectively SEQ I D NO.: 535-537 and 539-541; (xxxxviii) are SEQ ID NO.: 545-547 and 549-551 respectively; (xxxxix) are SEQ ID NO.: 555-557 and 559-561 respectively; (xxxxx ) are respectively SEQ ID NO.: 565-567 and 569-571; (xxxxxi) are respectively SEQ ID NO.: 575-577 and 579-581; (xxxxxii) are respectively SEQ ID NO.: 585, 586 or 625, 587 or 627, and 589-591; (xxxxxiii) are respectively SEQ ID NO.: 595-597 and 599-601; (xxxxxiv) are respectively SEQ ID NO.: 605-607 and 609-611; (xxxxxv) are respectively SEQ ID NO.: 615-617 and 619-621, (xxxxxvi) are SEQ ID NO.: 631, 632 or 635 or 637 or 639 or 641 or 643 or 645 or 647 or 649 or 651 or 653 or 655 or 657, respectively or 659 or 661 or 663 or 665 or 667 or 669 or 671 or 673 or 675 or 677 or 679 or 681 or 683 or 685, 633 and 697-699; (xxxxxvii) are SEQ ID NO.: 693-695 and 697 respectively -699; (xxxxxviii) is SEQ ID NO.: 400, 401, and any of 751, 753, 755, 757, or 760, and any of 404, 405, and 745 or 747, respectively; (xxxxxxix ) are SEQ ID NO.: 585, 586, and 762 or 764, and 589-591, respectively; or (xxxxxxx) are SEQ ID NO.: 400, 401, 766, and 404-406, respectively.

In any of the embodiments disclosed herein, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences according to: SEQ ID NO.: 631, 632, respectively or 635 or 637 or 639 or 641 or 643 or 645 or 647 or 649 or 651 or 653 or 655 or 657 or 659 or 661 or 663 or 665 or 667 or 669 or 671 or 673 or 675 or 677 or 679 or 681 or 683 or 685, 633 and 697-699. In any of the embodiments disclosed herein, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acids according to SEQ ID NO.: 693-695 and 697-699, respectively sequence.

In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NOs.: 400-402 and 404-406, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400, 401, 766, and 404-406, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400-402, 404, 405, and 745, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400, 401, 766, 404, 405, and 745, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400-402, 404, 405, and 747, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400, 401, 766, 404, 405, and 747, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400, 401, 751, and 404-406, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400, 401, 753, and 404-406, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400, 401, 755, and 404-406, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400, 401, 757, and 404-406, respectively. In certain embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, or CDRL3 amino acid sequence according to SEQ ID NO.: 400, 401, 760, and 404-406, respectively.

In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure comprise CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3, wherein each CDR is independently selected from the corresponding CDRs of: SARS-CoV-2 S2X16- v1 mAb, SARS-CoV-2 S2X16-v2 mAb, SARS-CoV-2 S2X16-v3 mAb, SARS-CoV-2 S2X16-v4 mAb, SARS-CoV-2 S2X16-v5 mAb, SARS-CoV-2 S2X16- v6 mAb, SARS-CoV-2 S2X16-v7 mAb, SARS-CoV-2 S2X16-v8 mA, b SARS-CoV-2 S2X28-v1 mAb, SARS-CoV-2 S2X30-v1 mAb, SARS-CoV-2 S2X30 -v2 mAb, SARS-CoV-2 S2X30-v3 mAb, SARS-CoV-2 S2X30-v4 mAb, SARS-CoV-2 S2X30-v5 mAb, SARS-CoV-2 S2X30-v6 mAb, SARS-CoV-2 S2X47 -v1 mAb, SARS-CoV-2 S2X47-v2 mAb, SARS-CoV-2 S2X47-v3 mAb, SARS-CoV-2 S2X47-v4 mAb, SARS-CoV-2 S2X47-v5 mAb, SARS-CoV-2 S2X47 -v6 mAb, SARS-CoV-2 S2X47-v7 mAb, SARS-CoV-2 S2X47-v8 mAb, SARS-CoV-2 S2X47-v9 mAb, SARS-CoV-2 S2X55-v1 mAb, SARS-CoV-2 S2X55 -v2 mAb, SARS-CoV-2 S2X56-v1 mAb, SARS-CoV-2 S2X58-v1 mAb, SARS-CoV-2 S2X58-v2 mAb, SARS-CoV-2 S2X71-v1 mAb SARS-CoV-2 S2X76- v1 mAb, SARS-CoV-2 S2X76-v2 mAb, SARS-CoV-2 S2X76-v3 mAb, SARS-CoV-2 S2X76-v4 mAb, SARS-CoV-2 S2X11-v1 mAb, or SARS-CoV-2 S2X35- v1 mAb, SARS-CoV-2 S2X35-v2 mAb, SARS-CoV-2 S2X35-v3 mAb, SARS -CoV-2 S2X35-v4 mAb, SARS-CoV-2 S2X35-v5 mAb, SARS-CoV-2 S2X35-v6 mAb, SARS-CoV-2 S2X35-v7 mAb, SARS-CoV-2 S2X35-v8 mAb, SARS -CoV-2 S2H30-v1 mAb, SARS-CoV-2 S2H37-v1 mAb, SARS-CoV-2 S2H40-v1 mAb, SARS-CoV-2 S2H58-v1 mAb, SARS-CoV-2 S2H58-v2 mAb, SARS -CoV-2 S2H58-v3 mAb, SARS-CoV-2 S2H58-v4 mAb, SARS-CoV-2 S2H58-v5 mAb, SARS-CoV-2 S2H58-v6 mAb, SARS-CoV-2 S2H58-v7 mAb, SARS -CoV-2 S2H62-v1 mAb, SARS-CoV-2 S2H62-v2 mAb, SARS-CoV-2 S2H62-v3 mAb, SARS-CoV-2 S2H66-v1 mAb, SARS-CoV-2 S2H66-v2 mAb, SARS -CoV-2 S2H66-v3 mAb, SARS-CoV-2 S2H70-v1 mAb, SARS-CoV-2 S2H71-v1 mAb, SARS-CoV-2 S2H73-v1 mAb, SARS-CoV-2 S2N12-v1 mAb, SARS -CoV-2 S2N12-v2 mAb, SARS-CoV-2 S2N12-v3 mAb, SARS-CoV-2 S2N22-v1 mAb, SARS-CoV-2 S2N22-v2 mAb, SARS-CoV-2 S2N22-v3 mAb, SARS -CoV-2 S2N22-v4 mAb, SARS-CoV-2 S2N22-v5 mAb, SARS-CoV-2 S2N22-v6 mAb, SARS-CoV-2 S2N22-v7 mAb, SARS-CoV-2 S2N25-v1 mAb, SARS -CoV-2 S2N28-v1 mAb, SARS-CoV-2 S2E6-v1 mAb, SARS-CoV-2 S2E7-v1 mAb, SARS-CoV-2 S2E9-v1 mAb, SARS-CoV-2 S2E12-v1 mAb, SARS -CoV-2 S2E12-v2 mAb, SARS-CoV-2 S2E13-v1 mAb , SARS-CoV-2 S2E14-v1 mAb, SARS-CoV-2 S2K4-v1 mAb, SARS-CoV-2 S2X193-v1 mAb, SARS-CoV-2 S2X195-v1 mAb, SARS-CoV-2 S2X219-v1 mAb , SARS-CoV-2 S2X244-v1 mAb, SARS-CoV-2 S2X246-v1 mAb, SARS-CoV-2 S2X256-v1 mAb, SARS-CoV-2 S2X269-v1 mAb, SARS-CoV-2 S2X278-v1 mAb , SARS-CoV-2 S2M7-v1 mAb, SARS-CoV-2 S2M11-v1 mAb, SARS-CoV-2 S2M16-v1 mAb, SARS-CoV-2 S2M28-v1 mAb, SARS-CoV-2 S2L49-v1 mAb , SARS CoV-2 S2D65-v1 mAb, SARS CoV-2 S2D97-v1 mAb, SARS CoV-2 S2D106-v1 mAb, SARS CoV-2 S2X149-v1 mAb, SARS CoV-2 S2X179-v1 mAb, SARS-CoV- 2 S2H101 mAb, an antibody 409_11_1_v2, antibody 409_11_1_v3, antibody 409_11_1_v4, antibody 409_11_1_v5, antibody 409_11_1_v6, antibody 409_11_2_v1, antibody 409_11_2_v2, antibody 409_11_2_v3, antibody 409_11_2_v4, antibody 409_11_2_v5, antibody 409_11_2_v6, antibody 409_11_2_v7, antibody 409_11_2_v8, antibody 409_11_2_v9, antibody 409_11_2_v10, antibody 409_11_2_v11, antibodies 409_11_2_v12, antibody 409_11_2_v13, antibody 409_11_2_v14, antibody 409_11_2_v15, antibody 409_11_2_v16, antibody 409_11_2_v17, antibody 409_11_2_v18, antibody 409_11_2_v19, antibody 409_11_2_v20, antibody 409_11_2_v21, antibody 409_11_2_v22, antibody 409_11_2_v23, antibody 409_11_2_v24, antibody 409_11_2_v25, antibody 409_11_2_v26, antibody 409_11_2_v27, Antibody 409_11_3_v1, Antibody 409_11 _4_v2, antibodies 409_11_4_v3, antibody 409_11_4_v4, antibody 409_11_4_v5, antibody 409_11_4_v6, antibody 409_11_4_v7, antibody 409_11_4_v8, antibody 409_11_4_v9, antibody 409_11_4_v10, antibody 409_11_4_v11, an antibody or antibody 409_11_4_v12 409_11_4_v13, as provided in Table 2. That is, all combinations of CDRs from the SARS-CoV-2 mAb and its variant sequences provided in Table 2 are encompassed.

During antibody development, DNA in germline variable (v), joining (J), and diversity (D) loci can rearrange and nucleotide insertions and/or deletions in coding sequences can occur. Somatic mutations can be encoded by the resulting sequences and can be identified by reference to corresponding known germline sequences. In some cases, the desired property of the antibody (eg, binding to a SARS-CoV-2 antigen) is not critical, or the antibody confers an undesired property (eg, increased immunogen in the individual to which the antibody is administered). Sexual risk) or somatic mutations of both can be substituted by the corresponding germline-encoded amino acid or by a different amino acid, so that the desired properties of the antibody are improved or maintained and the undesirable properties of the antibody are reduced or eliminated characteristic. Thus, in some embodiments, an antibody or antigen-binding fragment of the present disclosure comprises at least one more germline-encoded amino acid in the variable region than the parent antibody or antigen-binding fragment, with the proviso that The parent antibody or antigen-binding fragment contains one or more somatic mutations. The variable region and CDR amino acid sequences of the anti-SARS-CoV-2 antibodies of the present disclosure are provided in Table 2 herein.

Exemplary antibodies of the present disclosure include antibody S2E12 and engineered variants thereof. The engineered S2E12 variant includes "antibody 409_11_4_v2", "antibody 409_11_4_v3", "antibody 409_11_4_v4", "antibody 409_11_4_v5", "antibody 409_11_4_v6", "antibody 409_11_4_v7", "antibody 409_11_4_v8", "antibody 409_11_4_v8", "antibody 409_11_v8" ", "Antibody 409_11_4_v11", "Antibody 409_11_4_v12", "Antibody 409_11_4_v13". In particular embodiments, the antibody or antigen-binding fragment comprises a CDRH1, CDRH2, CDRH3, CDRH1, CDRH2, CDRH3, CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and/or CDRL3. Table 1 also provides amino acid sequences comprising the S2E12 CDRH3 sequence and the two amino acids (Ala-Ser) immediately N-terminal to CDRH3 in S2E12.

In some embodiments, the antibody or antigen-binding fragment comprises: the VH amino acid set forth in any one of SEQ ID NO.: 399, 748, 749, 750, 752, 754, 756, 758, 759, and 761 CDRH1, CDRH2 and/or CDRH3 of the sequence; and CDRL1, CDRL2 and/or CDRL3 of the VL amino acid sequence set forth in any one of SEQ ID NO.:403, 738, 744 and 746 (that is, according to Any CDR numbering or determination method known in the art, such as IMGT, Kabat, Chothia, AHo, North, Contact, CCG, EU or Martin (Enhanced Chothia)). For example, in some embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, and/or CDRH3 of the VH amino acid sequence set forth in SEQ ID NO.:399, and set forth in SEQ ID NO.:738 CDRL1, CDRL2 and/or CDRL3 of the VL amino acid sequence, wherein these CDRs are according to IMGT. As another non-limiting example, in some embodiments, the antibody or antigen-binding fragment comprises CDRH1, CDRH2, and CDRH3 of the VH amino acid sequence set forth in SEQ ID NO.:399, and in SEQ ID NO.:738 CDRL1, CDRL2 and CDRL3 of the VL amino acid sequence described, wherein these CDRs are according to IMGT.

In other embodiments, the antibody or antigen-binding fragment comprises at least 85% (eg, 85%, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%) identical VHs, and/or at least 85% (e.g., 85%, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%) identical VLs. In yet other embodiments, the antibody or antigen-binding fragment comprises a VH that is at least 90% identical to the VH amino acid sequence provided in Table 1 and/or has a VL amino acid sequence provided in Table 1 A VL of at least 90% identity. In yet other embodiments, the antibody or antigen-binding fragment comprises a VH that is at least 95% identical to the VH amino acid sequence provided in Table 1 and/or has a VL amino acid sequence provided in Table 1 A VL of at least 95% identity. In yet other embodiments, the antibody or antigen-binding fragment comprises a VH that is at least 99% identical to the VH amino acid sequence provided in Table 1 and/or has a VL amino acid sequence provided in Table 1 A VL of at least 99% identity. In some embodiments, the antibody or antigen-binding fragment comprises a VH amino acid sequence selected from the VH amino acid sequences provided in Table 1 and a VL amino acid selected from the VL amino acid sequences provided in Table 1 sequence. In some embodiments, the S2E12 antibody comprises a kappa light chain, eg, k1m3, IGKC*01. Table 1. CDRs ( IMGT ) and variable region amino acid sequences of certain S2E12 antibodies CDRH1 GFTFTSSA (SEQ ID NO.: 400) CDRH2 IVVGSGNT (SEQ ID NO.: 401) CDRH3 PYCSGGSCSDGFDI (SEQ ID NO.:766) PYCSGGSCSDAFDI (SEQ ID NO.:769) PYSSGGSSSDGFDI (SEQ ID NO.:770) PYPSGGSPSDGFDI (SEQ ID NO.:771) PYASGGSASDGFDI (SEQ ID NO.:772) PYCSGGSCSEGFDI (SEQ ID NO.:771) .:773) CDRH3 and N-terminal adjacent alanine and serine amino acids ASPYCSGGSCSDGFDI (SEQ ID NO.:402) ASPYCSGGSCSDAFDI (SEQ ID NO.:751) ASPYSSGGSSSDGFDI (SEQ ID NO.:753) ASPYPSGGSPSDGFDI (SEQ ID NO.:755) ASPYASGGSASDGFDI (SEQ ID NO.:757) ASPYCSGGSCSEGFDI (SEQ ID NO.:757) .:760) VH QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGWIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYCSGGSCSDGFDIWGQGTMVTVSS (SEQ ID NO.:399) QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGFIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYCSGGSCSDGFDIWGQGTMVTVSS (SEQ ID NO.:748) QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGYIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYCSGGSCSDGFDIWGQGTMVTVSS (SEQ ID NO.:749) QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGWIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYCSGGSCSDAFDIWGQGTMVTVSS (SEQ ID NO.:750) QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGWIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYSSGGSSSDGFDIWGQGTMVTVSS (SEQ ID NO.:752) QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGWIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYPSGGSPSDGFDIWGQGTMVTVSS (SEQ ID NO .:754) QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGWIVVGSGNTNYAQKFHERVTITRDMSTSTAMELSSLRSEDTAVYYCASPYASGGSASDGFDIWGQGTMVTVSS (SEQ ID NO.:756) QVQLVQSGPEVKKP GTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGFIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYCSGGSCSEGFDIWGQGTMVTVSS (SEQ ID NO.:758) QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGWIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYCSGGSCSEGFDIWGQGTMVTVSS (SEQ ID NO.:759) QVQLVQSGPEVKKPGTSVRVSCKASGFTFTSSAVQWVRQARGQRLEWVGAIVVGSGNTNYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCASPYCSGGSCSDGFDIWGQGTMVTVSS (SEQ ID NO.:761) CDRL1 QSVSSSY (SEQ ID NO.: 404) CDRL2 GAS (SEQ ID NO.: 405) CDRL3 QQYVGLTGWT (SEQ ID NO.:406) QQYVGLTGFT (SEQ ID NO.:745) QQYVGLTGYT (SEQ ID NO.:747) VL DIVLTQTPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYVGLTGWTFGQGTKVEIK (SEQ ID NO.:403) DIVLTQTPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRALIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYVGLTGWTFGQGTKVEIK (SEQ ID NO.:738) DIVLTQTPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYVGLTGFTFGQGTKVEIK (SEQ ID NO.:744) DIVLTQTPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYVGLTGYTFGQGTKVEIK (SEQ ID NO.:746)

In some embodiments, an antibody or antigen-binding fragment thereof comprises a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a complementarity determining region (CDR) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise or consist of the amino acid sequences set forth in (a) SEQ ID NO.: 400, 401, 766, 404, 405 and 406 respectively; (b) SEQ ID NO.: 400, 401, 769, 404, 405 and 406 respectively; (c) SEQ ID NO. : 400, 401, 770, 404, 405 and 406; (d) respectively SEQ ID NO.: 400, 401, 771, 404, 405 and 406; (e) respectively SEQ ID NO.: 400, 401, 772 , 404, 405 and 406; (f) are SEQ ID NO.: 400, 401, 773, 404, 405 and 406, respectively; (g) are SEQ ID NO.: 400, 401, 766, 404, 405 and 745, respectively (h) are respectively SEQ ID NO.: 400, 401, 769, 404, 405 and 745; (i) are respectively SEQ ID NO.: 400, 401, 770, 404, 405 and 745; (j) are respectively SEQ ID NO.: 400, 401, 771, 404, 405 and 745; (k) respectively SEQ ID NO.: 400, 401, 772, 404, 405 and 745; (l) respectively SEQ ID NO.: 400 , 401, 773, 405, 405 and 745; (m) are respectively SEQ ID NO.: 400, 401, 766, 404, 405 and 747; (n) are respectively SEQ ID NO.: 400, 401, 769, 404 , 405 and 747; (o) are SEQ ID NO.: 400, 401, 770, 404, 405 and 747, respectively; (p) are SEQ ID NO.: 400, 401, 771, 404, 405 and 747, respectively; ( q) is SEQ ID NO.: 400, 401, 772, 404, 405 and 747, respectively; or (r) is SEQ ID NO.: 400, 401, 773, 404, 405 and 747, respectively.

In other embodiments, the antibody or antigen-binding fragment comprises the amino acid sequences set forth in: (a) SEQ ID NO.: 400, 401, 402, 404, 405, and 406; (b) SEQ ID NO.: 400, 401, 751, 404, 405 and 406; (c) SEQ ID NO.: 400, 401, 753, 404, 405 and 406; (d) SEQ ID NO.: 400, 401, 755, 404, 405 and 406; (e) SEQ ID NO.: 400, 401, 757, 404, 405 and 406; (f) SEQ ID NO.: 400, 401, 760, 404, 405 and 406; (g) SEQ ID NO.: 400, 401, 402, 404, 405 and 745; (h) SEQ ID NO.: 400, 401, 751, 404, 405 and 745; (i) SEQ ID NO.: 400, 401, 753, 404, 405 and 745; (j) SEQ ID NO.: 400, 401, 755, 404, 405 and 745; (k) SEQ ID NO.: 400, 401, 757, 404, 405 and 745; (l) SEQ ID NO.: 400, 401, 760, 405, 405 and 745; (m) SEQ ID NO.: 400, 401, 402, 404, 405 and 747; (n) SEQ ID NO.: 400, 401, 751, 404, 405 and 747; (o) SEQ ID NO.: 400, 401, 753, 404, 405 and 747; (p) SEQ ID NO.: 400, 401, 755, 404, 405 and 747; (q) SEQ ID NO.: 400, 401, 757, 404, 405 and 747; or (r) SEQ ID NO.: 400, 401, 760, 404, 405 and 747. In each of (a)-(r) above, it is understood that the first three such SEQ ID NOs are VH amino acid sequences and the last three such SEQ ID NOs are VL amino acid sequences. For example, in (a), SEQ ID NO.: 400, 401 and 402 are the amino acid sequences in VH, and SEQ ID NO.: 404, 405 and 406 are the amino acid sequences in VL.

Other exemplary antibodies include S2M11, S2D106, S2H58 and engineered variants thereof. In some embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences as set forth in SEQ ID NOs.: 525-527 and 529-531, respectively. In other embodiments, the antibody or antigen-binding fragment comprises a VH and a VL having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or comprising or consisting of SEQ ID NO. : consists of the amino acid sequence set forth in SEQ ID NO.: 524, and the VL has at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99% or comprises or consists of SEQ ID NO.: 528 The amino acid sequence composition described.

In other embodiments, the antibody or antigen-binding fragment comprises as set forth in SEQ ID NO.: 585, 586, 587, 589, 590, and 591, respectively, or as set forth in SEQ ID NO.: 585, 625, 627, 589, respectively, CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in 590 and 591. In other embodiments, the antibody or antigen-binding fragment comprises a VH and a VL having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or comprising or consisting of SEQ ID NO. : the amino acid sequence composition set forth in any one of 584, 624, 626, and 628, and the VL has at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99% Either comprise or consist of the amino acid sequence set forth in SEQ ID NO.:588. In other embodiments, the antibody or antigen-binding fragment comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences as set forth in SEQ ID NO.: 229, 230, 231, 233, 234, and 235, respectively. In other embodiments, the antibody or antigen-binding fragment comprises a VH and a VL having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or comprising or consisting of SEQ ID NO. : the amino acid sequence composition set forth in any one of 228, 740, 741, 742, and 743, and the VL has at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99% either comprise or consist of the amino acid sequence set forth in SEQ ID NO.:232. In other embodiments, the antibody or antigen-binding fragment comprises a VH and a VL having at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or comprising or consisting of SEQ ID NO. : the amino acid sequence composition set forth in any one of 228, 740, 741, 742, and 743, and the VL has at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99% either comprise or consist of the amino acid sequence set forth in SEQ ID NO.:238.

In certain embodiments, the antibody or antigen-binding fragment comprises amino acid modifications (eg, substitution mutations) to eliminate the undesirable risks of oxidation, desamidation, and/or isomerization.

Variant antibodies provided herein include variants comprising one or more amino acid changes in variable regions (eg, VH, VL, backbone, or CDRs) compared to antibodies disclosed herein having specific sequences antibody, wherein the variant antibody is capable of binding to the SARS-CoV-2 antigen.

In certain embodiments, the VH comprises at least 85% (eg, 85%, 86%, 87%, 88%, 89%, 90%, 91%) with an amino acid sequence according to any of the following %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences or consist of: SEQ ID NO.: 22, 32 , 42, 52, 62, 72, 74, 84, 96, 106, 119, 129, 139, 150, 163, 173, 175, 178, 186, 189, 191, 198, 208, 218, 228, 240, 254 , 264, 274, 284, 298, 312, 322, 332, 350, 351, 353, 359, 361, 363, 365, 367, 368, 369, 379, 389, 399, 409, 419, 429, 434, 444 , 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 626, 628, 630, 634, 636, 638, 640 , 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 692, 740, 741 , 742, 743, 748, 749, 750, 752, 754, 756, 758, 759, 761, 762, and 765, wherein the change is optionally limited to one or more framework regions and/or the change comprises One or more substitutions of the encoded amino acid; and/or (ii) the VL comprises at least 85% (e.g., 85%, 86%, 87%) with the amino acid sequence according to any of the following , 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences or from Its composition: SEQ ID NO.: 26, 36, 46, 56, 66, 78, 88, 94, 100, 110, 123, 133, 143, 154, 157, 168, 194, 196, 202, 212, 222, 232, 238, 244, 250, 252, 258, 268, 278, 288, 294, 296, 302, 308, 310, 316, 326, 336, 355, 357, 373, 383, 393, 403, 413, 423, 438, 448, 458, 468, 478, 488, 498, 508, 518, 528, 538, 548, 558, 568, 57 8, 588, 598, 608, 618, 686, 696, 738, 744 and 746, wherein the change is optionally limited to one or more framework regions and/or the change comprises one of the amino acids encoded by the germline or multiple substitutions.

In other embodiments, the VH has at least 85% of the amino acid sequence set forth in any one of SEQ ID NO.: 399, 748, 749, 750, 752, 754, 756, 758, 759, and 761 (For example, with 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100 %) identity, and the VL has at least 85% (e.g., has 85%, 86%, 87%) with the amino acid sequence set forth in any one of SEQ ID NO. %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%).

In other embodiments, the VH has at least 85% of the amino acid sequence set forth in any one of SEQ ID NO.: 399, 748, 749, 750, 752, 754, 756, 758, 759, and 761 (For example, with 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100 %), and the VL has at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) consistency.

In other embodiments, the VH has at least 85% of the amino acid sequence set forth in any one of SEQ ID NO.: 399, 748, 749, 750, 752, 754, 756, 758, 759, and 761 (For example, with 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100 %), and the VL has at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) consistency.

In other embodiments, the VH has at least 85% of the amino acid sequence set forth in any one of SEQ ID NO.: 399, 748, 749, 750, 752, 754, 756, 758, 759, and 761 (For example, with 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100 %), and the VL has at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) consistency.

In other embodiments, the VH has at least 85% of the amino acid sequence set forth in any one of SEQ ID NO.: 399, 748, 749, 750, 752, 754, 756, 758, 759, and 761 (For example, with 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100 %), and the VL has at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) consistency.

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:399, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:399, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:399, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:399, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:748, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:748, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:748, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:748, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:749, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:749, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:749, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:749, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:750, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:750, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:750, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:750, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:750, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:752, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:752, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:752, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:754, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:754, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:754, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:754, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:756, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:756, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:756, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:756, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:758, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:758, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:758, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:758, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:759, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:759 and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:759, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:759, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:761 and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:403 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:761 and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:738 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:761 and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:744 . In some embodiments, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO.:761 and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:746 .

In some embodiments, the VH comprises or consists of any of the VH amino acid sequences set forth in Table 2, and the VL comprises or consists of any of the VL amino acid sequences set forth in Table 2. In particular embodiments, the VH and the VL comprise or consist of amino acid sequences according to: (i) SEQ ID NO.: 22 and 26, respectively; (ii) SEQ ID NO.: 32 and 36, respectively (iii) respectively SEQ ID NO.: 42 and 46; (iv) respectively SEQ ID NO.: 52 and 56; (v) respectively SEQ ID NO.: 62 and 66; (vi) respectively SEQ ID NO.: 72 and 66; (vii) respectively SEQ ID NO.: 74 and 78; (viii) respectively SEQ ID NO.: 84 and 88; (ix) respectively SEQ ID NO.: 84 and 94; ( x) are respectively SEQ ID NO.: 96 and 100; (xi) are respectively SEQ ID NO.: 106 and 110; (xii) are respectively SEQ ID NO.: 119 and 123; (xiii) are respectively SEQ ID NO. : 129 and 133; (xiv) are respectively SEQ ID NO.: 22 or 150 and 26, 154 or 157; (xv) are respectively SEQ ID NO.: 42 or 163 and 46 or 168; (xvi) are respectively SEQ ID NO.: any one of 129, 173, 175 or 178 and 133; (xvii) is any one of SEQ ID NO.: 52, 186, 189 or 191 and any one of 56, 194 or 196, respectively (xviii) are respectively SEQ ID NO.: 198 and 202; (xix) are respectively SEQ ID NO.: 208 and 212; (xx) are respectively SEQ ID NO.: 218 and 222; (xxi) are respectively SEQ ID NO.: 208 and 222 ID NO.: 228 and 232 or 238; (xxii) SEQ ID NO.: 240, respectively, and any one of 244, 250, or 252; (xxiii) SEQ ID NO.: 254 and 258, respectively; (xxiv) ) are respectively SEQ ID NO.: 264 and 268; (xxv) are respectively SEQ ID NO.: 274 and 278; (xxvi) are respectively SEQ ID NO.: 284, and any one of 288, 294 or 296; (xxvii) are respectively SEQ ID NO.: 298, and any one of 302, 308 or 310; (xxviii) are SEQ ID NO.: 312 and 316, respectively; (xxix) are SEQ ID NO.: 322 and 326; (xxx) are respectively SEQ ID NO.: 332 and 336, (xxxi) are respectively in SEQ ID NO.: 228, 350, 351 or 353 any one and any one of 232, 238, 355 or 357; (xxxii) are any one of SEQ ID NO.: 312, 359, 361, 363, 365, 367 or 368 and 316, respectively; ( xxxiii) are respectively SEQ ID NO.: 369 and 373; (xxxiv) are respectively SEQ ID NO.: 379 and 383; (xxxv) are respectively SEQ ID NO.: 389 and 393; (xxxvi) are respectively SEQ ID NO. : 399 and 403 or 738; (xxxvii) are respectively SEQ ID NO.: 409 and 413; (xxxviii) are respectively SEQ ID NO.: 419 and 423; (xxxix) are respectively SEQ ID NO.: 434 and 438; ( xxxx) are respectively SEQ ID NO.: 444 and 448; (xxxxi) are respectively SEQ ID NO.: 454 and 458; (xxxxii) are respectively SEQ ID NO.: 464 and 468; (xxxxiii) are respectively SEQ ID NO. : 474 and 478; (xxxxiv) are respectively SEQ ID NO.: 484 and 488; (xxxxv) are respectively SEQ ID NO.: 494 and 498; (xxxxvi) are respectively SEQ ID NO.: 504 and 508; (xxxxvii) are respectively SEQ ID NO.: 514 and 518; (xxxxviii) are respectively SEQ ID NO.: 524 and 528; (xxxix) are respectively SEQ ID NO.: 534 and 538; (xxxxx) are respectively SEQ ID NO.: 544 and 548; (xxxxxi) are respectively SEQ ID NO.: 554 and 558; (xxxxxii) are respectively SEQ ID NO.: 564 and 568; (xxxxxiii) are respectively SEQ ID NO.: 574 and 578; (xxxxxiv) are respectively SEQ ID NO.: 584 and 588; (xxxxxv) are respectively SEQ ID NO.: 594 and 598; (xxxxxvi) are respectively SEQ ID NO.: 604 and 608; (xxxxxvii) are respectively SEQ ID NO.: 614 and 618 (xxxxxviii) are respectively SEQ ID NO.: 624, 626 or 628 and 588; (xxxxxix) are respectively SEQ ID NO.: 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652 , 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682 or 684 and 686; (xxxxxx) are respectively SEQ ID NO.: 692 and 696; (xxxxxxi) are respectively SEQ ID NO.: 740-743 Any one of and 238; (xxxxxxii) are any of SEQ ID NO.: 399, 748, 749, 750, 752, 754, 756, 758, 759 or 761 and any of 403, 744 or 746, respectively one; or (xxxxxxiii) are SEQ ID NO.: 762 or 764 and 588, respectively.

In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 624, 626 or 628 and 588, respectively. In certain embodiments, VH and VL comprise or consist of amino acid sequences according to the following, respectively: SEQ ID NO.: 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682 or 684 and 686. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 692 and 696, respectively.

In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 399 and 738, respectively.

In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 399 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 399 and 738, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 399 and 744, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 399 and 746, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 748 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 749 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 750 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 752 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 754 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 756 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 758 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 759 and 403, respectively. In certain embodiments, VH and VL comprise or consist of the amino acid sequences according to SEQ ID NO.: 761 and 403, respectively.

The term "CL" refers to "immunoglobulin light chain constant region" or "light chain constant region", ie, the constant region from an antibody light chain. The term "CH" refers to "immunoglobulin heavy chain constant region" or "heavy chain constant region", which can be further divided into CH1, CH2 and CH3 (IgA, IgD, IgG) or CH1, CH2, CH3 according to antibody isotype, and CH4 domain (IgE, IgM). The Fc region of an antibody heavy chain is further described herein. In any of the embodiments disclosed herein, the antibody or antigen-binding fragment of the present disclosure comprises any one or more of CL, CH1, CH2, and CH3. In certain embodiments, the CL comprises 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% with the amino acid sequence SEQ ID NO.:8 or SEQ ID NO.:9 %, 98%, 99% or 100% identical amino acid sequences. In certain embodiments, CH1-CH2-CH3 (also referred to as CH1-CH3) comprises 90%, 91%, 92%, 93%, 90%, 91%, 92%, 93% identical to the amino acid sequence SEQ ID NO.:6 or SEQ ID NO.:7 %, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical amino acid sequences.

In certain embodiments, an antibody or antigen-binding fragment of the present disclosure comprises a heavy chain polypeptide and a light chain polypeptide, the heavy chain polypeptide comprising or consisting of the amino acid sequence set forth in SEQ ID NO.:767, and the The light chain polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO.:768.

It is understood that one or more C-terminal lysines of an antibody heavy chain can be removed, eg, in mammalian cell lines produced (see eg, Liu et al., mAbs 6(5):1145-1154 (2014)). Accordingly, an antibody or antigen-binding fragment of the present disclosure may comprise a heavy chain, CH1-CH3, CH3 or Fc polypeptide with or without the presence of a C-terminal lysine residue; in other words, encompassed therein heavy chain, CH1-CH3 or Fc Examples in which the C-terminal residue of the polypeptide is removed from the C-terminal lysine instead of lysine, and in which the lysine is the C-terminal residue. In certain embodiments, a composition comprises a plurality of antibodies and/or antigen-binding fragments of the present disclosure, wherein one or more antibodies or antigen-binding fragments are not included at the C-terminus of a heavy chain, CH1-CH3, or Fc polypeptide and wherein one or more of the antibody or antigen-binding fragments comprises a lysine residue at the C-terminus of the heavy chain, CH1-CH3, or Fc polypeptide. In other words, in certain embodiments, the heavy chain may comprise or consist of the amino acid sequence set forth in SEQ ID NO.:767 without a C-terminal lysine. In certain embodiments, the heavy chain or CH1-CH3 may comprise the amino acid sequence set forth in SEQ ID NO.:6 or SEQ ID NO.:7 without a C-terminal lysine.

A "Fab" (antigen-binding fragment) is a portion of an antibody that binds to an antigen and includes the variable region and CH1 of the heavy chain linked to the light chain via interchain disulfide bonds. Each Fab fragment is monovalent with respect to antigen binding, that is, it has a single antigen binding site. Treatment of the antibody with pepsin yields a single large F(ab')2 fragment, which roughly corresponds to a two disulfide-linked Fab fragment that has bivalent antigen binding activity and is still capable of crosslinking the antigen. Both Fab and F(ab')2 are examples of "antigen-binding fragments". Fab' fragments differ from Fab fragments in that Fab' fragments have an additional few residues at the carboxy terminus of the CH1 domain, including one or more cysteines from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine residues of the constant domains have free thiol groups. F(ab')2 antibody fragments were originally produced as pairs of Fab' fragments with hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

Fab fragments can be joined, eg, by peptide linkers, to form single-chain Fabs, also referred to herein as "scFabs." In these embodiments, the interchain disulfide bonds present in the native Fab may not be present, and the linker is used, in whole or in part, to link or link Fab fragments in a single polypeptide chain. Heavy chain derived Fab fragments (e.g., comprising, consisting of, or consisting essentially of VH + CH1 or "Fd") and light chain derived Fab fragments (e.g., (comprising, consisting of, or consisting essentially of VL+CL) can be linked in any arrangement to form a scFab. For example, scFabs can be arranged in an N-terminal to C-terminal direction according to (heavy chain Fab fragment-linker-light chain Fab fragment) or (light chain Fab fragment-linker-heavy chain Fab fragment). Peptide linkers and exemplary linker sequences for use in scFabs are discussed in more detail herein.

"Fv" is a small antibody fragment containing complete antigen recognition and antigen binding sites. This fragment typically consists of a dimer of a heavy chain variable region and a light chain variable region in tight, non-covalent association. However, even if a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) is capable of recognizing and binding an antigen, it is usually with lower affinity than the entire binding site.

"Single-chain Fv" (also abbreviated "sFv" or "scFv") are antibody fragments comprising _VH and _VL antibody domains linked into a single polypeptide chain. In some embodiments, the scFv polypeptide comprises a polypeptide linker between the VH and VL domains that enables the scFv to form the desired structure for antigen binding. Such peptide linker sequences can be incorporated into fusion polypeptides using standard techniques well known in the art. For a review of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, Vol. 113, eds. Rosenburg and Moore, Springer-Verlag, New York, pp. 269-315 (1994); Borrebaeck 1995, infra. In certain embodiments, the antibody or antigen-binding fragment comprises a scFv comprising a VH domain, a VL domain, and a peptide linker connecting the VH domain to the VL domain. In particular embodiments, the scFv comprises a VH domain linked to a VL domain by a peptide linker, which may be in a VH-linker-VL orientation or in a VL-linker-VH orientation. Any scFv of the present disclosure can be engineered such that the C-terminus of the VL domain is linked to the N-terminus of the VH domain by a short peptide sequence, or vice versa (ie, (N)VL(C)-linker-(N) )VH(C) or (N)VH(C)-Linker-(N)VL(C). Alternatively, in some embodiments, the linker can be attached to the N-terminal portion of the VH domain, the VL domain, or both or end.

The peptide linker sequence can be selected, for example, based on (1) its ability to assume a flexible, extended configuration; (2) its inability or lack of presentation to interact with the first and second polypeptides and/or on the target molecule. The ability of the functional epitope to interact with the secondary structure; and/or (3) the lack or relative lack of hydrophobic or charged residues that may react with the polypeptide and/or the target molecule. Other considerations regarding linker design (eg, length) can include the configuration or range of configurations in which VH and VL can form a functional antigen binding site. In certain embodiments, the peptide linker sequence contains, for example, Gly, Asn, and Ser residues. Other nearly neutral amino acids such as Thr and Ala may also be included in the linker sequence. Other amino acid sequences suitable for use as linkers include those disclosed in: Maratea et al, Gene 40:3946 (1985); Murphy et al, Proc. Natl. Acad. Sci. USA 83:8258 8262 ( 1986); US Patent No. 4,935,233 and US Patent No. 4,751,180. Other illustrative and non-limiting examples of linkers can include, for example, Glu-Gly-Lys-Ser-Ser-Gly-Ser-Gly-Ser-Glu-Ser-Lys-Val-Asp (SEQ ID NO: 19) (Chaudhary et al, Proc. Natl. Acad. Sci. USA 87:1066-1070 (1990)) and Lys-Glu-Ser-Gly-Ser-Val-Ser-Ser-Glu-Gln-Leu-Ala-Gln-Phe- Arg-Ser-Leu-Asp (SEQ ID NO: 20) (Bird et al., Science 242: 423-426 (1988)) and pentameric Gly-Gly-Gly-Gly-Ser (SEQ ID NO: 21), When present in a single iteration or repeated 1 to 5 or more times, or higher; see eg, SEQ ID NO: 17. Any suitable linker can be used, and in general lengths can be about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 15 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100 amino acids, or less than about 200 amino acids in length acid, and will preferably comprise a flexible structure (which can provide flexibility and space for conformational movement between two regions, domains, motifs, segments or modules connected by a linker), and will preferably be biologically inert and/or low risk of immunogenicity in humans. Exemplary linkers include linkers comprising or consisting of the amino acid sequences set forth in any one or more of SEQ ID NOs: 10-21. In certain embodiments, the linker comprises at least 75% (i.e., at least about 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or higher) identical amino acid sequences or consist thereof.

scFvs can be constructed using any combination of VH and VL sequences disclosed herein or any combination of CDRHl, CDRH2, CDRH3, CDRLl, CDRL2 or CDRL3 sequences.

In some embodiments, a linker sequence is not required; eg, when the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate functional domains and prevent steric interference.

In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure are monospecific (eg, bind to a single epitope) or multispecific (eg, bind to multiple epitopes and/or target molecules). Antibodies and antigen-binding fragments can be constructed in a variety of formats. Exemplary antibody formats are disclosed in Spiess et al., Mol. Immunol. 67(2):95 (2015), and in Brinkmann and Kontermann, mAbs 9(2):182-212 (2017), the formats thereof and Methods of preparation are incorporated herein by reference and include, for example, Bispecific T-Cell Engagers (BiTEs), DARTs, Knob-Hole (KIH) Modules, scFv-CH3-KIH Modules, KIH Common Light Chain Antibodies, TandAbs, Trisomy (Triple Bodies), TriBi Mini Antibodies, Fab-scFv, scFv-CH-CL-scFv, F(ab')2-scFv2, Tetravalent HCabs, Intrabodies, CrossMabs, Bifunctional Fabs (DAFs) (2 in 1) or four in one), DutaMabs, DT-IgG, charge pairs, Fab arm exchange, SEEDbodies, Triomabs, LUZ-Y modules, Fcabs, κλ-bodies, orthogonal Fabs, DVD-Igs (e.g., US Pat. No. 8,258,268 , the form of which is incorporated herein by reference in its entirety), IgG(H)-scFv, scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv , IgG(H)-V, V(H)-IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody and DVI- IgG (four-in-one), as well as so-called FIT-Ig (eg, PCT Publication No. WO 2015/103072, the format of which is incorporated herein by reference in its entirety), the so-called WuxiBody format (eg, PCT Publication No. WO 2015/103072 WO 2019/057122, the form of which is incorporated herein by reference in its entirety) and the so-called In-Elbow-Insert Ig form (IEI-Ig, eg, PCT Publication Nos. WO 2019/024979 and WO 2019/025391, which form is incorporated herein by reference in its entirety).

In certain embodiments, the antibody or antigen-binding fragment comprises a VH domain, two or more VL domains, or both (ie, two or more VH domains and two or more VL domains) two or more of them. In certain embodiments, the antigen-binding fragment comprises the form (N-terminal to C-terminal orientation) VH-linker-VL-linker-VH-linker-VL, wherein the two VH sequences may be the same or different, and the two The VL sequences may be the same or different. Such linked scFvs can include any combination of VH and VL domains configured to bind to a given target, and in a form comprising two or more VHs and/or two or more VLs, can bind one, two or more different epitopes or antigens. It will be appreciated that formats incorporating multiple antigen binding domains may include VH and/or VL sequences in any combination or orientation. For example, an antigen-binding fragment can comprise the form VL-Linker-VH-Linker-VL-Linker-VH, VH-Linker-VL-Linker-VL-Linker-VH or VL-Linker-VH -Linker-VH-Linker-VL.

Constructed monospecific or multispecific antibodies or antigen-binding fragments of the present disclosure comprise any combination of VH and VL sequences disclosed herein and/or any combination of CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 sequences. In some embodiments, bispecific or multispecific antibodies or antigen-binding fragments may comprise one, two, or more antigen-binding domains (eg, VH and VL) of the present disclosure. There may be two or more binding domains that bind to the same or different SARS-CoV-2 epitopes, and in some embodiments, bispecific or multispecific antibodies or antigen-binding fragments as provided herein may comprise Another SARS-CoV-2 binding domain, and/or may comprise binding domains that bind together to different antigens or pathogens.

In any of the embodiments disclosed herein, the antibody or antigen-binding fragment may be multispecific; eg, bispecific, trispecific, or the like.

In certain embodiments, the antibody or antigen-binding fragment comprises: (i) a first VH and a first VL; and (ii) a second VH and a second VL, wherein the first VH and the second VH are different and each independently comprise at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%) of the amino acid sequence set forth in any of the following %, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical monoamino acid sequences: SEQ ID NO.: 22, 32, 42, 52, 62, 72, 74, 84, 96, 106, 119, 129, 139, 150, 163, 173, 175, 178, 186, 189, 191, 198, 208, 218, 228, 240, 298, 312, 322, 332, 350, 351, 353, 359, 361, 363, 365, 367, 368, 369, 379, 389, 399, 409, 419, 429, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 626, 628, 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 692, 740, 741, 742, 743, 748, 749, 750, 752, 754, 756, 758, 759, 761, 762, and 764, and wherein the first VL and the second VL are different and each independently comprise at least 85% of the amino acid sequence set forth in any of the following (e.g., having 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) Sexual amino acid sequence: SEQ ID NO.: 26, 36, 46, 56, 66, 78, 88, 94, 100, 110, 123, 133, 143, 154, 157, 168, 194, 196, 202, 212, 222, 232, 238, 244, 250, 252, 258, 268, 278, 288, 294, 296, 302, 308, 310, 316, 326, 336, 355, 357, 373, 383, 393, 403, 413, 423, 438, 448, 458, 468, 478, 488, 498, 508, 518, 528, 538, 548, 558, 568 , 578, 588, 598, 608, 618, 686, 696, 738, 744, and 746, and wherein the first VH and the first VL together form a first antigen-binding site, and wherein the second VH and the first The two VLs together form the second antigen binding site.

In certain embodiments, the antibody or antigen-binding fragment comprises (i) a first VH and a first VL; and (ii) a second VH and a second VL, wherein the first VH comprises and SEQ ID NO.: 139 and The amino acid sequence set forth in any one of 342 has at least 85% (e.g., has 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%) %, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences, and the first VL comprises and SEQ ID NO.: 143 and 346 in any one of The stated amino acid sequence has at least 85% (e.g., has 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96% , 97%, 98%, 99% or 100%) identical amino acid sequence, and wherein the second VH comprises and SEQ ID NO.: 399, 748, 749, 750, 752, 754, 756, 758, The amino acid sequence set forth in any of 759 and 761 has at least at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences, and the second VL comprises the The amino acid sequence set forth in any one has at least a %, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences.

In certain embodiments, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof. An "Fc" fragment or Fc polypeptide comprises the carboxy-terminal portions of two antibody H chains (ie, the CH2 and CH3 domains of IgG) held together by disulfide bonds. Antibody "effector functions" refer to those biological activities attributable to the Fc region (eg, native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vary with antibody isotype. Examples of antibody effector functions include: Clq binding and complement-dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; downregulation of cell surface receptors (eg, B cell receptors) ; and B cell activation. As discussed herein, modifications (eg, amino acid substitutions) to the Fc domain can be made in order to alter (eg, improve, reduce, or eliminate) one or more functionalities of an Fc-containing polypeptide (eg, an antibody of the present disclosure) . Such functions include, for example, Fc receptor (FcR) binding, antibody half-life modulation (eg, by binding to FcRn), ADCC function, protein A binding, protein G binding, and complement binding. Amino acid modifications that alter (e.g., improve, reduce or eliminate) Fc functionality include, e.g. P331S, E333A, S239D/A330L/I332E, P257I/Q311, K326W/E333S, S239D/I332E/G236A, N297Q, K322A, S228P, L235E + E318A/K320A/K322A, L234A/L235A (also referred to herein as "LALA" ") and L234A/L235A/P329G mutations, which are summarized and annotated in InvivoGen (2011) and published at invivogen.com/PDF/review/review-Engineered-Fc-Regions-invivogen.pdf?utm_source=review&utm_medium= pdf&utm_campaign=review&utm_content=Engineered-Fc-Regions "Engineered Fc Regions" are available online and are incorporated herein by reference in their entirety.

For example, to activate the complement cascade, the C1q protein complex can bind to at least two molecules of IgG1 or one molecule of IgM when an immunoglobulin molecule is attached to an antigenic target (Ward, E.S. and Ghetie, V., Ther. Immunol. 2 (1995) 77-94). Burton, D. R. describes (Mol. Immunol. 22 (1985) 161-206) that the heavy chain region comprising amino acid residues 318 to 337 is involved in complement fixation. Duncan, A. R. and Winter, G. (Nature 332 (1988) 738-740) reported using site-directed mutagenesis that Glu318, Lys320 and Lys322 form a binding site to C1q. The role of Glu318, Lys320 and Lys322 residues in C1q binding was demonstrated by the ability of short synthetic peptides containing these residues to inhibit complement-mediated lysis.

For example, FcR binding can be mediated by the interaction of the Fc portion (the Fc portion of an antibody) with an Fc receptor (FcR), a specialized cell surface receptor on cells including hematopoietic cells . Fc receptors belong to the immunoglobulin superfamily and have been shown to mediate the removal of antibody-coated pathogens by phagocytosis of immune complexes and the lysis of erythrocytes and corresponding antibody-coated cells by antibody-dependent cell-mediated cytotoxicity. Both various other cellular targets (eg tumor cells) (ADCC; Van de Winkel, JG, and Anderson, CL, J. Leukoc. Biol. 49 (1991) 511-524). FcRs are defined by their specificity for immunoglobulin classes; Fc receptors for IgG antibodies are called FcγRs, for IgE FcεRs, for IgA FcαRs, etc., and neonatal Fc receptors are called FcγRs FcRn. Fc receptor binding is described, for example, in Ravetch, JV, and Kinet, JP, Annu. Rev. Immunol. 9 (1991) 457-492; Capel, PJ, et al, Immunomethods 4 (1994) 25-34; de Haas, M ., et al, J Lab. Clin. Med. 126 (1995) 330-341; and Gessner, JE, et al, Ann. Hematol. 76 (1998) 231-248.

Cross-linking of receptors to the Fc domain (FcyR) of native IgG antibodies triggers a variety of effector functions, including phagocytosis, antibody-dependent cytotoxicity, and release of inflammatory mediators, as well as immune complex clearance and modulation of antibody production. Contemplated herein are Fc moieties that provide cross-linking of receptors (eg, FcyRs). In humans, three classes of FcγRs have been characterized so far, which are: (i) FcγRI (CD64), which binds monomeric IgG with higher affinity and is Expressed on leukocytes; (ii) FcγRII (CD32), which binds complexed IgG with moderate to low affinity, is especially widely expressed on leukocytes, is believed to be a central player in antibody-mediated immunity, and can be divided into FcγRIIA , FcγRIIb, and FcγRIIC, which perform different functions in the immune system, but bind to IgG-Fc with lower affinity, and the extracellular domains of these receptors are highly homologous; and (iii) FcγRIII (CD16), which is characterized by Binds IgG with moderate to lower affinity and has been found in two forms: FcγRIIIA, which has been found on NK cells, macrophages, eosinophils and some monocytes and T cells and is believed to mediate ADCC; and FcγRIIIB, which Highly expressed on neutrophils.

FcyRIIA is found on many cells involved in killing (eg macrophages, monocytes, neutrophils) and appears to be able to activate the killing process. FcγRIIB appears to play a role in the inhibition process and is found on B cells, macrophages and on mast cells and eosinophils. Importantly, it has been shown that 75% of all FcyRIIbs are found in the liver (Ganesan, L. P. et al., 2012: "FcyRIIb on liver sinusoidal endothelium clears small immune complexes" Journal of Immunology 189: 4981-4988). FcγRIIB is well expressed on the hepatic sinusoidal endothelium (known as LSEC) and is a major site of clearance of small immune complexes in the liver and Kupffer cells in the LSEC (Ganesan, L. P. et al., 2012: FcγRIIb on liver sinusoidal endothelium clears small immune complexes. Journal of Immunology 189: 4981-4988).

In some embodiments, the antibodies and antigen-binding fragments thereof disclosed herein comprise Fc polypeptides or fragments thereof, such as IgG-type antibodies, for binding to FcyRIIb, particularly the Fc region. In addition, it is possible by introducing as described in Chu, S. Y. et al., 2008: Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcgammaRIIb with Fc-engineered antibodies. Molecular Immunology 45, 3926-3933 The mutations S267E and L328F engineered the Fc portion to promote FcyRIIb binding. Thereby, the clearance of immune complexes can be enhanced (Chu, S. et al., 2014: Accelerated Clearance of IgE In Chimpanzees Is Mediated By Xmab7195, An Fc-Engineered Antibody With Enhanced Affinity For Inhibitory Receptor FcγRIIb. Am J Respir Crit, American Thoracic Society International Conference Abstracts). In some embodiments, the antibodies or antigen-binding fragments thereof of the present disclosure comprise an engineered Fc portion with mutations S267E and L328F, inter alia, as described in: Chu, S. Y. et al., 2008: Inhibition of B cell receptor-mediated Activation of primary human B cells by coengagement of CD19 and FcgammaRIIb with Fc-engineered antibodies. Molecular Immunology 45, 3926-3933.

On B cells, FcyRIIb can be used to inhibit further immunoglobulin production and isotype switching to, for example, the IgE class. On macrophages, FcyRIIb is thought to inhibit phagocytosis, eg mediated through FcyRIIA. On eosinophils and mast cells, the B form can help inhibit the activation of these cells through IgE binding to its individual receptors.

Regarding FcyRI binding, modifications in the native IgG of at least one of E233-G236, P238, D265, N297, A327 and P329 reduced binding to FcyRI. Substitution of IgG2 residues at positions 233-236 in corresponding positions IgG1 and IgG4 reduced IgG1 and IgG4 binding to FcγRI by a factor of ¹⁰³ and abolished the response of human monocytes to antibody-sensitized erythrocytes (Armour, KL, et al. Eur. J. Immunol. 29 (1999) 2613-2624).

With regard to FcyRII binding, decreased binding was found for FcyRIIA, eg, IgG mutations for at least one of E233-G236, P238, D265, N297, A327, P329, D270, Q295, A327, R292, and K414.

The two allelic forms of human FcγRIIA are the "H131" variant, which binds to IgGl Fc with higher affinity; and the "R131" variant, which binds to IgGl Fc with lower affinity. See, eg, Bruhns et al., Blood 113:3716-3725 (2009).

Regarding FcγRIII binding, decreased binding to FcγRIIIA was found, for example, for E233-G236, P238, D265, N297, A327, P329, D270, Q295, A327, S239, E269, E293, Y296, V303, A327, K338 and D376 at least one mutation. Mapping the binding site of the Fc receptor on human IgG1, the mutation sites described above, and methods for measuring FcyRI and FcyRIIA binding are described in Shields, R. L. et al., J. Biol. Chem. 276 (2001) 6591-6604 .

The two allelic forms of human FcγRIIIA are the "F158" variant, which binds to IgGl Fc with lower affinity; and the "V158" variant, which binds to IgGl Fc with higher affinity. See, eg, Bruhns et al., Blood 113:3716-3725 (2009).

Regarding binding to FcyRII, two regions of native IgG Fc appear to be involved in the interaction between FcyRIIs and IgG, namely (i) the lower hinge site of the IgG Fc, especially the amino acid residues L, L, G, G (234- 237, EU numbering), and (ii) adjacent regions of the CH2 domain of an IgG Fc, particularly adjacent loops and bands in the upper CH2 domain (e.g., in the P331 region) of the lower hinge region (Wines, B.D., et al., J. Immunol. 2000; 164: 5313-5318). Furthermore, FcγRI appears to bind to the same site on IgG Fc, whereas FcRn and Protein A bind to different sites on IgG Fc, which appear to be at the CH2-CH3 interface (Wines, B.D., et al., J. Immunol. 2000 ; 164: 5313-5318).

Also encompassed are mutations that increase the binding affinity of an Fc polypeptide or fragment thereof of the present disclosure to (i.e., one or more) Fcγ receptors (eg, with a reference Fc polypeptide or fragment thereof or containing a mutation that does not contain one or more mutations). polypeptides or fragments thereof). See, eg, Delillo and Ravetch, Cell 161(5):1035-1045 (2015) and Ahmed et al, J. Struc. Biol. 194(1):78 (2016), Fc mutations and techniques thereof are incorporated by reference into this article.

In any of the embodiments disclosed herein, the antibody or antigen-binding fragment can comprise an Fc polypeptide or fragment thereof comprising a mutation selected from the group consisting of G236A; S239D; A330L and I332E; or comprising any of these mutations A combination of two or more; for example, S239D/I332E; S239D/A330L/I332E; G236A/S239D/I332E; G236A/A330L/I332E (also referred to herein as "GAALIE"); or G236A/S239D/A330L/ I332E. In some embodiments, the Fc polypeptide or fragment thereof does not comprise S239D.

In certain embodiments, the Fc polypeptide or fragment thereof may comprise or consist of at least a portion of the Fc polypeptide or fragment thereof involved in binding to FcRn. In certain embodiments, the Fc polypeptide or fragment thereof comprises an improved binding affinity for (eg, promotes binding to) FcRn (eg, at a pH of about 6.0), and in some embodiments, thereby extending the Fc polypeptide comprising One or more amino acid modifications for the in vivo half-life of the molecule or fragment thereof (eg, as compared to a reference Fc polypeptide or fragment thereof, or an antibody that is otherwise identical but does not contain the modification(s). In certain embodiments, the Fc polypeptide or fragment thereof comprises or is derived from an IgG Fc, and the half-life extending mutation comprises any one or more of the following: M428L; N434S; N434H; N434A; N434S; M252Y; S254T; T256E ; T250Q; P257I; Q311I; D376V; T307A; E380A (EU number). In certain embodiments, the half-life extending mutation comprises M428L/N434S (also referred to herein as "MLNS"). In certain embodiments, the half-life extending mutation comprises M252Y/S254T/T256E. In certain embodiments, the half-life extending mutation comprises T250Q/M428L. In certain embodiments, the half-life extending mutation comprises P257I/Q311I. In certain embodiments, the half-life extending mutation comprises P257I/N434H. In certain embodiments, the half-life extending mutation comprises D376V/N434H. In certain embodiments, the half-life extending mutation comprises T307A/E380A/N434A.

In some embodiments, the antibody or antigen-binding fragment includes an Fc portion comprising the substitution mutation M428L/N434S. In some embodiments, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof comprising substitutional mutations G236A/A330L/I332E. In certain embodiments, the antibody or antigen-binding fragment includes a (eg, IgG) Fc portion that includes the G236A mutation, the A330L mutation, and the I332E mutation (GAALIE), and does not include the S239D mutation (eg, includes the native S at position 239). ). In particular embodiments, the antibody or antigen-binding fragment includes an Fc polypeptide or fragment thereof comprising substitutional mutations: M428L/N434S and G236A/A330L/I332E, and optionally S239D. In certain embodiments, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof comprising substitutional mutations: M428L/N434S and G236A/S239D/A330L/I332E.

In certain embodiments, the antibody or antigen-binding fragment comprises a glycosylation-altering mutation, wherein the glycosylation-altering mutation comprises N297A, N297Q, or N297G, and/or the antibody or antigen-binding fragment is partially or fully deglycosylated and/or partial or complete defucosylation. Host cell lines and methods for making partially or fully deglycosylated or partially or fully defucosylated antibodies and antigen-binding fragments are known (see, eg, PCT Publication No. WO 2016/181357; Suzuki et al. . Clin. Cancer Res. 13(6):1875-82 (2007); Huang et al. MAbs 6:1-12 (2018)).

In certain embodiments, the antibody or antigen-binding fragment is detected even when no detectable level of the antibody or antigen-binding fragment is found in the individual (ie, when the antibody or antigen-binding fragment has been cleared from the individual after administration ), can also elicit sustained protection in vivo in individuals. Such protection is referred to herein as vaccine effect. Without wishing to be bound by theory, it is believed that dendritic cells can internalize complexes of antibody and antigen and subsequently induce or contribute to an endogenous immune response against the antigen. In certain embodiments, the antibody or antigen-binding fragment comprises one or more modifications, such as mutations in Fc, including G236A, A330L, and I332E, which are capable of activating dendrites that can induce, for example, T-cell immunity to antigens shape cells.

In any of the embodiments disclosed herein, the antibody or antigen-binding fragment comprises an Fc polypeptide or fragment thereof comprising CH2 (or fragment thereof), CH3 (or fragment thereof), or CH2 and CH3, wherein the CH2 , CH3, or both may be of any isotype and may contain amino acid substitutions or other modifications compared to the corresponding wild-type CH2 or CH3, respectively. In certain embodiments, an Fc polypeptide of the present disclosure comprises two CH2-CH3 polypeptides that associate to form a dimer.

In any of the embodiments disclosed herein, the antibody or antigen-binding fragment can be a monoclonal antibody or antigen-binding fragment. As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies (ie, the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts in some cases) . Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, each monoclonal antibody is directed against a single epitope of an antigen, as opposed to polyclonal antibody preparations that include different antibodies directed against different epitopes. In addition to their specificity, monoclonal antibodies are also advantageous in that they can be synthesized uncontaminated by other antibodies. The term "monoclonal" should not be construed as requiring the production of antibodies by any particular method. For example, monoclonal antibodies suitable for use in the present invention can be prepared by the fusion tumor method first described by Kohler et al., Nature 256:495 (1975), or recombinant DNA can be used in bacterial, eukaryotic or plant cells method (see, eg, US Pat. No. 4,816,567). Monoclonals can also be isolated from phage antibody libraries using techniques such as those described in Clackson et al., Nature, 352:624-628 (1991) and Marks et al., J. Mol. Biol., 222:581-597 (1991) Antibody. Monoclonal antibodies can also be obtained using the methods disclosed in PCT Publication No. WO 2004/076677A2.

Antibodies and antigen-binding fragments of the present disclosure include "chimeric antibodies" in which a portion of the heavy and/or light chain is identical or homologous to the corresponding sequence in an antibody derived from a particular species or belonging to a particular antibody class or subclass, and the remainder of the chain(s) is identical or identical to the corresponding sequence in an antibody derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies (so long as they exhibit the desired biological activity) source (see US Patent Nos. 4,816,567; 5,530,101 and 7,498,415; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)). For example, a chimeric antibody can comprise human and non-human residues. In addition, chimeric antibodies may contain residues not found in either the recipient antibody or the donor antibody. These modifications are made to further improve antibody performance. For additional details, see Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 ( 1992). Chimeric antibodies also include primatized and humanized antibodies.

A "humanized antibody" is generally regarded as a human antibody having one or more amino acid residues introduced therein from a non-human source. These non-human amino acid residues are typically obtained from variable domains. Humanization can follow the method of Winter and colleagues (Jones et al, Nature, 321:522-525 (1986); Reichmann et al, Nature, 332:323-327 (1988); Verhoeyen et al, Science, 239:1534 -1536 (1988)), by substituting non-human variable sequences for the corresponding sequences of human antibodies. Accordingly, such "humanized" antibodies are chimeric antibodies (US Pat. Nos. 4,816,567; 5,530,101 and 7,498,415) in which substantially less than complete human variable domains have been substituted with corresponding sequences from non-human species. In certain instances, a "humanized" antibody is an antibody produced by a non-human cell or animal and comprising human sequences, such as an _HC domain.

A "human antibody" is an antibody that contains only the sequences present in antibodies produced by humans. However, as used herein, human antibodies may contain residues or modifications not found in naturally occurring human antibodies (eg, antibodies isolated from humans), including those modified and variant sequences described herein. These are achieved in order to further improve or enhance antibody performance. In certain instances, human antibodies are produced by transgenic animals. See, for example, US Patent Nos. 5,770,429; 6,596,541 and 7,049,426.

In certain embodiments, the antibodies or antigen-binding fragments of the present disclosure are chimeric, humanized, or human antibodies or antigen-binding fragments.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of binding to SARS-CoV-2 surface glycoproteins with the following EC50s: less than 500 ng/ml, less than 250 ng/ml, less than 100 ng/ml ml, below 90 ng/ml, below 80 ng/ml, below 70 ng/ml, below 60 ng/ml, below 50 ng/ml, below 40 ng/ml, below 30 ng/ml , below 25 ng/ml, below 20 ng/ml, below 16 ng/ml, below 15 ng/ml, below 14 ng/ml, below 13 ng/ml, below 12 ng/ml, Below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 ng/ml, below 4 ng/ml or low At 2 mg/ml, as measured by ELISA (optionally, indirect ELISA and/or sandwich ELISA) and/or by flow cytometry, wherein the SARS CoV-2 surface glycoprotein is expressed on host cells on the cell surface.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of binding to the SARS-CoV-2 surface glycoprotein RBD with the following EC50: less than 500 ng/ml, less than 250 ng/ml, less than 100 ng /ml, below 90 ng/ml, below 80 ng/ml, below 70 ng/ml, below 60 ng/ml, below 50 ng/ml, below 40 ng/ml, below 30 ng/ml ml, less than 25 ng/ml, less than 20 ng/ml, less than 16 ng/ml, less than 15 ng/ml, less than 14 ng/ml, less than 13 ng/ml, less than 12 ng/ml , less than 10 ng/ml, less than 9 ng/ml, less than 8 ng/ml, less than 7 ng/ml, less than 6 ng/ml, less than 5 ng/ml, less than 4 ng/ml or Below 2 mg/ml, as measured by ELISA (optionally, indirect ELISA and/or sandwich ELISA) and/or by flow cytometry, wherein the SARS CoV-2 surface glycoprotein is expressed in the host on the cell surface of cells.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of binding to the SARS-CoV-2 RBD with the following KDs: less than 5 x ^10-8 M, less than 4 x ^10-8 M, less than 3 ×10 ^-8 M, below 2 × 10 ^-8 M, below 1 × 10 ^-8 M, below 5 × 10 ^-9 M, below 1 × 10 ^-9 M, below 5 × 10 ^-10 M , below 1×10 ^-10 M, below 5×10 ^-11 M, below 1×10 ^-11 M, below 5×10 ^-12 M, or below 1×10 ^-12 M if using biolayers Interferometry (BLI), optionally determined using an Octet instrument in which antibody or antigen-binding fragment is optionally loaded on a protein A needle at 2.7 µg/ml and SARS-CoV-2 RBD at 6 µg /ml, 1.5 µg/ml or 0.4 µg/ml for 5 minutes, further optionally measuring dissociation for 7 minutes.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of binding to the SARS-CoV-2 RBD with the following KDs: below 6×10 ⁻⁸ M, below 5×10 ⁻⁸ M, below 4 ×10 ^-8 M, below 3×10 ^-8 M, below 2×10 ^-8 M, below 1×10 ^-8 M, below 5×10 ^-9 M, below 4×10 ^-9 M , below 3×10 ^-9 M, below 2×10 ^-9 M, below 1×10 ^-9 M or below 8×10 ^-10 M, if using surface plasmon resonance (SPR), optional were determined using a single cycle kinetic method using a Biacore T200 instrument.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of binding to the SARS-CoV-2 RBD and inhibiting the interaction between (i) the RBD and (ii) human ACE2 and/or human SIGLEC-1.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of neutralizing: (i) infection by a SARS-CoV-2 pseudovirus, optionally: (i) (a) wherein the neutralization IC50 is low below 100 ng/ml, below 90 ng/ml, below 80 ng/ml, below 70 ng/ml, below 60 ng/ml, below 50 ng/ml, below 40 ng/ml, below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 15 ng/ml, below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 ng/ml, below 4 ng/ml, below 3 ng/ml, below 2 ng/ml or below 1 ng/ml, preferably below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 ng/ml, below 4 ng/ml, below 3 ng/ml, less than 2 ng/ml, or less than 1 ng/ml and/or (i)(b) wherein neutralization IC80 is less than 100 ng/ml, less than 90 ng/ml, less than 80 ng/ml , below 70 ng/ml, below 60 ng/ml, below 50 ng/ml, below 40 ng/ml, below 30 ng/ml or below 25 ng/ml, preferably below 50 ng/ml ml, less than 40 ng/ml, less than 30 ng/ml, or less than 25 ng/ml, and/or (i)(c) wherein the neutralization EC90 is less than 300 ng/ml, less than 200 ng/ml, Below 100 ng/ml, Below 90 ng/ml, Below 80 ng/ml, Below 70 ng/ml, Below 60 ng/ml 50 ng/ml, Below 40 ng/ml, Below 30 ng /ml, less than 25 ng/ml, less than 20 ng/ml, less than 15 ng/ml, or less than 10 ng/ml, wherein further optionally, the SARS-CoV-2 pseudovirus comprises VSV pseudovirus and and/or MLV pseudovirus, and/or (i)(d) the SARS-CoV-2 pseudovirus comprises VSV pseudovirus and/or MLV pseudovirus; and/or (ii) caused by live SARS-CoV-2 Infection, optionally (ii)(a) wherein the EC50 is below 60 ng/ml, below 50 ng/ml, below 40 ng/ml, below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 15 ng/ml, below 12 ng/ml, below 11 ng/ml, below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng /ml, less than 5/ng ml or less than 4 ng/ml, preferably less than 15 ng/ml, less than 12 ng/ml, less than 11 ng/ml, less than 10 ng/ml, less than 9 ng/ml, less than 8 ng/ml, less than 7 ng/ml, less than 6 ng/ml, less than 5/ng ml or less than 4 ng/ml and/or (ii)(b) wherein the EC90 is low below 50 ng/ml, below 40 ng/ml, below 35 ng/ml, below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 15 ng/ml, below 12 ng/ml, below 11 ng/ml, below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 /ng ml or less than 4 ng/ml, preferably less than 30 ng/ml, less than 25 ng/ml, less than 20 ng/ml, less than 15 ng/ml or less than 12 ng/ml, and/ or (ii) (c) over a 6-hour period with an infection multiplier of 0.1; and/or (iii) by expression, a host optionally engineered to overexpress DC-SIGN, L-SIGN, SIGLEC, or ACE2 Infection of live SARS-CoV-2 in cells (eg, HEK293T cells); and/or (iv) by expression, host cells (eg, HEK293T cells) optionally engineered to overexpress SIGLEC-1 or ACE2 ) infection of live SARS-CoV-2, wherein neutralizing infection includes fully neutralizing infection.

In some embodiments, an antibody or antigen-binding fragment of the present disclosure is capable of neutralizing by comprising the following mutations in a SARS-CoV-2 surface glycoprotein comprising SEQ ID NO.:3 as compared to the surface glycoprotein Infection of any of the SARS-CoV-2 variants: N501Y; S477N; N439K; L452R; E484K; K417N; T478K; S494P; A520S; N501T; A522S; Y453F; P384L.

In some embodiments, an antibody or antigen-binding fragment of the present disclosure is capable of neutralizing SARS at a lower rate than the antibody or antigen-binding fragment by comprising the surface glycoprotein amino acid sequence set forth in SEQ ID NO.:3 Infection with CoV-2 was 3 times more potent than infection by the SARS-CoV-2 variant.

In some embodiments, an antibody or antigen-binding fragment of the present disclosure is capable of activating FcyRIIa, FcyRIIIa, or both, wherein optionally: (i) the FcyRIIa comprises a H131 counterpart; and/or (ii) the FcyRIIIa comprises a V158 counterpart Gene; and/or (iii) activation is determined using target cells expressing SARS-CoV-2 S, such as CHO cells, and reporter cells expressing NFAT-driven reporters, such as luciferase.

In some embodiments, the in vivo half-life of an antibody or antigen-binding fragment of the present disclosure in a non-human primate is between 20 and 30 days, or between 22 and 28 days, or between 23 and 27 days between, or between 24 and 26 days, or about 25 days.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of neutralizing SARS-CoV-2 infection and/or neutralizing infection of target cells with an IC50 of about 20 to about 30 ng/ml.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of neutralizing SARS-CoV-2 infection and/or neutralizing infection of target cells with an IC50 of about 10 to about 20 ng/ml.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of neutralizing SARS-CoV-2 infection and/or neutralizing infection of target cells with an IC50 of about 5 to about 10 ng/ml.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of neutralizing SARS-CoV-2 infection and/or neutralizing infection of target cells with an IC50 of about 1 to about 5 ng/ml.

In some embodiments, the antibodies or antigen-binding fragments of the present disclosure are capable of neutralizing infection by SARS-CoV-2 and do not compete with human ACE2 for binding to the SARS-CoV-2 S protein, wherein optionally , which includes neutralizing infection in an in vitro infection model.

In some embodiments, an antibody or antigen-binding fragment of the present disclosure is provided that competes with the antibody or antigen-binding fragment of the present disclosure for binding to a SARS-CoV-2 surface glycoprotein. Polynucleotides, Vectors and Host Cells

In another aspect, the present disclosure provides isolated polynucleotides encoding the disclosed antibodies, or antigen-binding fragments thereof, or portions thereof (eg, CDRs, VH, VL, heavy or light chains) either. In certain embodiments, polynucleotides are codon-optimized for expression in host cells. When the coding sequence is known or identified, codon optimization can be performed using known techniques and tools, eg, using the GenScript® OptimiumGene ^™ tool; see also Scholten et al., Clin. Immunol. 119:135, 2006). Codon-optimized sequences include partially codon-optimized (ie, one or more codons optimized for performance in a host cell) and fully codon-optimized sequences.

It should also be appreciated that the polynucleotides encoding antibodies and antigen-binding fragments of the present disclosure may have different nucleotide sequences, but still encode the same antibodies or antigen-binding fragments due to, for example, brevity of the genetic code, splicing, and the like.

In certain embodiments, a polynucleotide comprises at least 50% (ie, 50%, 55%, 60%, 65%, 70%) of a polynucleotide sequence according to any one or more of the following %, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) consistent polynuclei Glycosides: SEQ ID NO.: 30, 31, 40, 41, 50, 51, 60, 61, 70, 71, 73, 82, 83, 92, 93, 95, 104, 105, 114, 115, 116, 117, 118, 127, 128, 137, 138, 206, 207, 216, 217, 226, 227, 236, 237, 239, 248, 249, 251, 253, 262, 263, 272, 273, 282, 283, 292, 293, 295, 297, 306, 307, 309, 311, 320, 321, 330, 331, 340, 341, 377, 378, 387, 388, 397, 398, 407, 408, 417, 418, 427, 428, 433, 442, 443, 452, 453, 462, 463, 472, 473, 482, 483, 492, 493, 502, 503, 512, 513, 552, 523, 532, 533, 542, 543, 552, 553, 562, 563, 572, 573, 582, 583, 592, 593, 602, 603, 612, 613, 622, 623, 690, 691, 700-737 and 739.

In certain embodiments, the polynucleotide comprises (i) at least 50%, at least 55%, at least 60%, at least 65%, at least 70% of the nucleotide sequence set forth in SEQ ID NO.:407 %, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identical, or comprising the nucleotide set forth in SEQ ID NO.:407 and (ii) have at least 50%, at least 55%, at least 60%, at least 65% with the nucleotide sequence set forth in SEQ ID NO.: 408, 737 or 739 %, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identical, or comprising SEQ ID NO.: 408, 737 or 739 A polynucleotide of the nucleotide sequence set forth in or consisting of.

In any of the embodiments disclosed herein, the polynucleotide may comprise deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). In some embodiments, the RNA comprises messenger RNA (mRNA).

A vector is also provided, wherein the vector comprises or contains a polynucleotide as disclosed herein (eg, a polynucleotide encoding an antibody or antigen-binding fragment that binds to SARS-CoV-2). The carrier may comprise any one or more of the carriers disclosed herein. In particular embodiments, a vector is provided comprising, eg, a DNA plastid construct encoding an antibody or antigen-binding fragment or portion thereof (eg, a so-called "DMAb"; see eg, Muthumani et al., J Infect Dis. 214 (3 ): 369-378 (2016); Muthumani et al, Hum Vaccin Immunother 9:2253-2262 (2013)); Flingai et al, Sci Rep. 5:12616 (2015); and Elliott et al, NPJ Vaccines 18 (2017 ), antibody-encoding DNA constructs thereof and related methods of use, including administration of antibody-encoding DNA constructs, incorporated herein by reference). In certain embodiments, the DNA plastid construct comprises a single open reading frame encoding the heavy and light chains (or VH and VL) of an antibody or antigen-binding fragment, wherein the sequence encoding the heavy chain and the sequence encoding the light chain are either are optionally separated by polynucleotides encoding protease cleavage sites and/or by polynucleotides encoding self-cleaving peptides. In some embodiments, the substituent component of the antibody or antigen-binding fragment is encoded by a polynucleotide contained in a single plastid. In other embodiments, the substituted component of the antibody or antigen-binding fragment is comprised of two or more plastids (eg, the first plastid comprises a polynucleotide encoding a heavy chain, VH, or VH+CH, And the second plastid comprises the polynucleotide encoding in the polynucleotide encoding the homologous light chain, VL or VL+CL. In certain embodiments, a single plastid comprises polynucleotides encoding heavy and/or light chains from two or more antibodies or antigen-binding fragments of the present disclosure. An exemplary expression vector is pVax1, available from Invitrogen®. DNA plastids of the present disclosure can be delivered to an individual, eg, by electroporation (eg, intramuscular electroporation) or by an appropriate formulation (eg, hyaluronidase).

In another aspect, the present disclosure also provides a host cell expressing an antibody or antigen-binding fragment according to the present disclosure; or comprising or containing a vector or polynucleotide according to the present disclosure.

Examples of such cells include, but are not limited to, eukaryotic cells, such as yeast cells, animal cells, insect cells, plant cells; and prokaryotic cells, including E. coli. In some embodiments, the cells are mammalian cells. In certain such embodiments, the cells are mammalian cell lines, such as CHO cells (eg, DHFR-CHO cells (Urlaub et al., PNAS 77:4216 (1980)), human embryonic kidney cells (eg, HEK293T cells) , PER.C6 cells, Y0 cells, Sp2/0 cells. NSO cells, human liver cells, e.g., Hepa RG cells, myeloma cells, or fusionoma cells. Other examples of mammalian host cell lines include mouse Sertoli Monkey kidney cells (e.g., TM4 cells); monkey kidney CV1 strain transformed by SV40 (COS-7); baby hamster kidney cells (BHK); African green monkey kidney cells (VERO-76); monkey kidney cells (CV1); human Cervical cancer cells (HELA); human lung cells (W138); human liver cells (Hep G2); canine kidney cells (MDCK; buffalo mouse liver cells (BRL 3A); mouse mammary tumor (MMT 060562); TRI cells; and FS4 cells. Mammalian host cell lines suitable for antibody production also include those described, for example, in Yazaki and Wu, Methods in Molecular Biology, Vol. 248 (eds. B.K.C. Lo, Humana Press, Totowa, N.J.), Vol. 255 - those host cell lines in p. 268 (2003).

In certain embodiments, the host cell is a prokaryotic cell, such as E. coli. The expression of peptides in prokaryotic cells such as E. coli is well established (see, eg, Pluckthun, A. Bio/Technology 9:545-551 (1991). For example, antibodies can be produced in bacteria without the need for glycosylation and This is especially true for Fc effector functions. For the expression of antibody fragments and polypeptides in bacteria, see, eg, US Pat. Nos. 5,648,237; 5,789,199; and 5,840,523.

In particular embodiments, cells can be transfected with expression vectors using vectors according to the present specification. The term "transfection" refers to the introduction of a nucleic acid molecule, such as a DNA or RNA (eg, mRNA) molecule, into a cell, eg, a eukaryotic cell. In the context of this specification, the term "transfection" encompasses any method known to those skilled in the art for introducing nucleic acid molecules into cells, such as eukaryotic cells, including mammalian cells. Such methods encompass, for example, electroporation, transfection of liposomes based on, for example, cationic lipids and/or liposomes, calcium phosphate precipitation, nanoparticle-based transfection, virus-based transfection, or cationic polymer-based (such as DEAE-Polymer) Glucose or polyethyleneimine, etc.) transfection. In certain embodiments, the introduction is non-viral.

Furthermore, host cells of the present disclosure can be stably or transiently transfected with vectors according to the present disclosure, eg, for expressing antibodies or antigen-binding fragments thereof according to the present disclosure. In such embodiments, cells can be stably transfected with a vector as described herein. Alternatively, cells can be transiently transfected with a vector according to the present disclosure encoding an antibody or antigen-binding fragment as disclosed herein. In any of the embodiments disclosed herein, the polynucleotide can be heterologous to the host cell.

Accordingly, the present disclosure also provides recombinant host cells that heterologously express the antibodies or antigen-binding fragments of the present disclosure. For example, the cells may be of a different species than the species from which the antibody was obtained, in whole or in part, (eg, CHO cells expressing human antibodies or engineered human antibodies). In some embodiments, the host cell is a cell type that does not express the antibody or antigen-binding fragment in nature. In addition, the host cell can confer translation on an antibody or antigen-binding fragment that is not present in the native state of the antibody or antigen-binding fragment (or in the native state in which the antibody or antigen-binding fragment is engineered or a parent antibody derived therefrom) Post-modification (PTM; eg glycosylation or fucosylation). Such PTMs can produce functional differences (eg, reduced immunogenicity). Thus, an antibody or antigen-binding fragment of the present disclosure produced by a host cell may include one or more post-translational modifications that differ from the antibody (or parent antibody) in its native state (eg, a human antibody produced by CHO cells) Can comprise one or more post-translational modifications that differ from the antibody when isolated from humans and/or produced by native human B cells or plasma cells).

Insect cells suitable for expressing the binding proteins of the present disclosure are known in the art and include, for example, Spodoptera frugiperda Sf9 cells, Spodoptera frugiperda BTI-TN5B1-4 cells, and Spodoptera frugiperda SfSWT01 "Mimic™" cells . See, eg, Palmberger et al., J. Biotechnol. 153(3-4):160-166 (2011). Numerous baculovirus strains have been identified that can be used in combination with insect cells, especially for transfection of Spodoptera frugiperda cells.

Eukaryotic microorganisms such as filamentous fungi or yeast are also suitable hosts for colonization or expression of protein-encoding vectors, including those whose glycosylation pathway has been "humanized" to allow the production of antibodies with partially or fully human glycosylation patterns. Fungal and yeast strains. See Gerngross, Nat. Biotech. 22:1409-1414 (2004); Li et al., Nat. Biotech. 24:210-215 (2006).

Plant cells can also be used as hosts for expressing the binding proteins of the present disclosure. For example, the PLANTIBODIES™ technology (described in, eg, US Pat. Nos. 5,959,177; 6,040,498; 6,420,548; 7,125,978; and 6,417,429) employs transgenic plants to produce antibodies.

In certain embodiments, the host cells comprise mammalian cells. In specific embodiments, the host cells are CHO cells, HEK293 cells, PER.C6 cells, Y0 cells, Sp2/0 cells, NSO cells, human liver cells, myeloma cells, or fusionoma cells.

In a related aspect, the present disclosure provides methods for producing antibodies or antigen-binding fragments, wherein the methods comprise culturing the host cells of the present disclosure under conditions and for a time sufficient to produce the antibodies or antigen-binding fragments. For example, methods suitable for isolating and purifying recombinantly produced antibodies can include obtaining supernatants from a suitable host cell/vector system that secretes recombinant antibodies into the culture medium, and then concentrating using commercially available filters culture medium. After concentration, the concentrate can be applied to a single suitable purification matrix or to a series of suitable matrices, such as affinity matrices or ion exchange resins. One or more reverse phase HPLC steps can be used to further purify the recombinant polypeptide. These purification methods can also be used when the immunogen is isolated from its natural environment. Methods for large-scale production of one or more of the isolated/recombinant antibodies described herein include batch cell culture that is monitored and controlled to maintain appropriate culture conditions. Purification of soluble antibodies can be performed according to methods described herein and known in the art, and consistent with the laws and guidelines of domestic and foreign regulatory agencies. composition

Also provided herein are any one or more of the disclosed antibodies, antigen-binding fragments, polynucleotides, vectors or host cells, alone or in any combination, and may further comprise pharmaceutically acceptable A composition of carriers, excipients or diluents. Carriers, excipients, and diluents are discussed in further detail herein.

In certain embodiments, a composition comprises two or more different antibodies or antigen-binding fragments according to the present disclosure. In certain embodiments, the antibodies or antigen-binding fragments to be used in combination each independently have any one or more of the following characteristics: neutralize naturally occurring SARS-CoV-2 variants; do not compete with each other Spike protein binding; binds to different Spike protein epitopes; reduced formation of resistance to SARS-CoV-2; reduced formation of resistance to SARS-CoV-2 when combined; strongly neutralizes live SARS -CoV-2 virus; exhibits additive or synergistic effects on live SARS-CoV-2 virus when used in combination; exhibits effector function; is protective in SARS-CoV-2; can be produced in sufficient quantities for large-scale production.

In certain embodiments, the composition comprises two or more different antibodies or antigen-binding fragments, which can be two or more of the antibodies or antigen-binding fragments disclosed herein. In any of the embodiments disclosed herein, an antibody or antigen-binding fragment thereof may be included in a composition further comprising an antibody or antigen-binding fragment comprising: (i) SEQ ID NO: 1, respectively The CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in ID NO.: 343-345 and 347-349; or (ii) as in SEQ ID NO.: 140-142 and 144-146, respectively The CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences as set forth; or (iii) the VH and VL amino acid sequences as set forth in SEQ ID NO.: 342 and 346, respectively; or (iv) as The VH and VL amino acid sequences are set forth in SEQ ID NO.: 139 and 143, respectively.

In certain embodiments, the composition comprises a first antibody or antigen-binding fragment and a second antibody or antigen-binding fragment, the first antibody or antigen-binding fragment comprising a VH and a VL, the VH comprising or consisting of SEQ ID NO: 32 The amino acid sequence set forth consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 36; and the second antibody or antigen-binding fragment comprises VH and VL, which VH comprises or consists of SEQ ID NO: 36 consists of the amino acid sequence set forth in ID NO: 139, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 143. In certain embodiments, the composition comprises a first antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL) comprising CDRH1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein the CDRH1, CDRH2 and CDRH3 respectively comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 33-35, And the CDRL1, CDRL2 and CDRL3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 37-39, respectively, and a second antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light A chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprising CDRL1, CDRL2 and CDRL3, wherein the CDRH1, CDRH2 and CDRH3 respectively comprise The amino acid sequences set forth in SEQ ID NOs: 140-142 or consist of the same, and the CDRL1, CDRL2 and CDRL3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 144-146, respectively.

In certain embodiments, the composition comprises a first antibody or antigen-binding fragment and a second antibody or antigen-binding fragment, the first antibody or antigen-binding fragment comprising a VH and a VL, the VH comprising or consisting of, for example, SEQ ID NO: 139 or the amino acid sequence set forth in 342, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 143 or 346; and the second antibody or antigen-binding fragment comprises VH and VL, The VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 399, 748, 749, 750, 752, 754, 756, 758, 759 or 761, and the VL comprises or consists of SEQ ID NO: 403, The amino acid sequence composition set forth in 744 or 746. In certain embodiments, the composition comprises a first antibody or antigen-binding fragment and a second antibody or antigen-binding fragment, the first antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain ( VL), the heavy chain variable domain (VH) comprises CDRH1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein the CDRH1, CDRH2 and CDRH3 comprise SEQ ID NO: 140 respectively - 142 or the amino acid sequences set forth in 343-345, respectively, or consist of, and the CDRL1, CDRL2, and CDRL3, respectively, comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 144-146; and The second antibody or antigen-binding fragment comprises a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprises CDRH1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2, and CDRL3, wherein the CDRH1, CDRH2, and CDRH3 comprise the amino acid sequence set forth in any one of SEQ ID NOs: 400, 401, and 751, 753, 755, 757, 760, respectively, or consists of, and the CDRL1, CDRL2 and CDRL3 comprise or consist of the amino acid sequence set forth in any of SEQ ID NOs: 404, 405 and 406, 745 and 747, respectively.

Also provided herein is a composition comprising: (i) a first antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with the group consisting of ACE2, DC - the interaction between the first cell surface receptors of SIGN, L-SIGN and SIGLEC-1; and (ii) a second antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein and inhibiting The interaction between the SARS-CoV-2 surface glycoprotein and a second cell surface receptor selected from ACE2, DC-SIGN, L-SIGN and SIGLEC-1, wherein the first cell surface receptor and the second cell surface receptor Cell surface receptors are different. As taught in the present invention, antibodies or antigen-binding fragments can be combined with SARS-CoV-2 to inhibit SARS-CoV-2 and two or more cell surface receptors by combining antibodies or antigen-binding fragments; e.g. Interactions between adhesion receptors and entry receptors, two entry receptors, two adhesion receptors or analogs thereof to achieve or improve neutralization of infection. Methods of using such antibody combinations to treat or prevent SARS-CoV-2 infection are also provided.

In certain embodiments, a composition includes a first vector and a second vector, the first vector includes a first plastid, and the second vector includes a second plastid, wherein the first plastid includes an encoded antibody or its The heavy chain, VH or VH+CH polynucleotide of the antigen-binding fragment, and the second plastid comprises the polynucleotide encoding the cognate light chain, VL or VL+CL. In certain embodiments, the composition comprises a polynucleotide (eg, mRNA) coupled to a suitable delivery vehicle or carrier. Exemplary vehicles or carriers for administration to human subjects include lipid or lipid source-derived delivery vehicles, such as liposomes, solid lipid nanoparticles, oily suspensions, submicron lipid emulsions, lipid microvesicles, Inverse lipid micelles, cochlear liposomes, lipid microtubules, lipid micropillars or lipid nanoparticles (LNPs) or nanoscale platforms (see e.g. Li et al. Wilery Interdiscip Rev. Nanomed Nanobiotechnol. 11(2):e1530 (2019)). Principles, reagents and techniques for designing appropriate mRNAs and formulating mRNA-LNPs and their delivery are described, for example, in Pardi et al. (J Control Release 217345-351 (2015)); Thess et al. (Mol Ther 23: 1456-1464 ( 2015)); Thran et al (EMBO Mol Med 9(10):1434-1448 (2017); et al (Sci. Immunol. 4 eaaw6647 (2019); and Sabnis et al (Mol. Ther. 26:1509-1519) (2018)), such techniques include capping, codon optimization, nucleoside modification, mRNA purification, incorporation of mRNA into stable lipid nanoparticles (e.g., ionizable cationic lipids/phosphatidylcholine/ Cholesterol/PEG-lipid; ionizable lipid: distearyl PC: cholesterol: polyethylene glycol lipid), and subcutaneous, intramuscular, intradermal, intravenous, intraperitoneal and intratracheal administration thereof, by reference Incorporated herein. Methods and uses

Also provided herein are methods of diagnosing SARS-CoV-2 infection (eg, in a human subject or in a sample obtained from a human subject) using the antibodies or antigen-binding fragments, nucleic acids, vectors, cells, or compositions of the present disclosure.

A diagnostic method (eg, in vitro, in vitro) can include contacting an antibody, antibody fragment (eg, an antigen-binding fragment) with a sample. Such samples can be isolated from an individual, eg, obtained from, eg, nasal passages, sinus cavities, salivary glands, lungs, liver, pancreas, kidneys, ears, eyes, placenta, digestive tract, heart, ovary, pituitary, adrenal gland, thyroid, brain , isolated tissue samples of skin or blood. Methods of diagnosis may also include detection of antigen/antibody complexes, especially after contacting the antibody or antibody fragment with the sample. Such detection steps are carried out on a laboratory bench, that is, without any contact with the human or animal body. Examples of detection methods are well known to those skilled in the art and include, for example, enzyme-linked immunosorbent assays (ELISAs), including direct, indirect, and sandwich ELISAs. Other detection methods include, but are not limited to, immunohistochemistry (IHC), flow cytometry (eg, FACS), western blotting, immunocytochemistry (ICC), enzyme-linked immunospot (ELISPOT), and immunoprecipitation (IP). Antibodies and antigen-binding fragments used in detection methods can be, for example, fluorescently or otherwise detectably labeled (eg, directly conjugated to a fluorophore or comprising a fluorophore secondary conjugate).

Also provided herein are methods of using an antibody or antigen-binding fragment of the present disclosure, or a composition comprising the antibody or antigen-binding fragment, to treat a subject, wherein the subject has, is believed to have, or is at risk of developing an infection caused by SARS-CoV-2 under risk. "Treat," "treatment," or "amelioration" refers to an individual (eg, a human or non-human mammal, such as a primate, horse, cat, dog, goat, mouse, or rat) The medical management of the disorder, disease or condition of the patient. In general, an appropriate dose or treatment regimen comprising an antibody or composition of the present disclosure is administered in an amount sufficient to elicit a therapeutic or prophylactic benefit. Therapeutic or prophylactic/prophylactic benefits include improved clinical outcomes; alleviation or relief of disease-related symptoms; reduced occurrence of symptoms; improved quality of life; longer disease-free state; reduced disease severity; stabilization of disease condition ; delay or prevent disease progression; remission; survival; extended survival; or any combination thereof. In certain embodiments, a therapeutic or prophylactic/prophylactic benefit includes reducing or preventing (ie, in a statistically significant manner) hospitalizations for treatment of SARS-CoV-2 infection. In certain embodiments, the therapeutic or prophylactic/prophylactic benefit includes reducing the duration of hospitalization for treatment of SARS-CoV-2 infection (ie, in a statistically significant manner). In certain embodiments, the therapeutic or prophylactic/prophylactic benefit includes reducing or eliminating the need for respiratory interventions, such as intubation and/or use of a ventilator device. In certain embodiments, the therapeutic or prophylactic/prophylactic benefit includes advanced disease pathology and/or reduced mortality.

A "therapeutically effective amount" or "effective amount" of an antibody, antigen-binding fragment, polynucleotide, vector, host cell, or composition of the present disclosure refers to an amount of the composition or molecule sufficient to produce a therapeutic effect, and the treatment Effects include improved clinical outcomes in a statistically significant manner; alleviation or alleviation of disease-related symptoms; reduction in the occurrence of symptoms; improved quality of life; longer disease-free state; reduction in disease severity; stabilization of disease condition; Delay or prevent disease progression; remission; survival or prolonged survival. When referring to an individual active ingredient administered alone, a therapeutically effective amount refers to the effect of that ingredient or the cells that express that ingredient alone. When referring to a combination, a therapeutically effective amount refers to the combined amount of the active ingredient that produces the therapeutic effect or the combined adjunct active ingredient and the cells expressing the active ingredient, whether administered consecutively, sequentially or simultaneously. A combination can comprise, for example, two different antibodies that specifically bind to a SARS-CoV-2 antigen, which in certain embodiments can be the same or different SARS-CoV-2 antigens, and/or can comprise the same or different epitopes.

Accordingly, in certain embodiments, methods are provided for treating a SARS-CoV-2 infection in an individual, wherein the methods comprise administering to the individual an effective amount of an antibody, antigen-binding fragment, poly(antigen-binding fragment) as disclosed herein. Nucleotides, vectors, host cells or compositions.

In general, subjects that can be treated by the present disclosure are human and other primate subjects, such as monkeys and apes used for veterinary purposes. Other model organisms such as mice and rats can also be treated in accordance with the present disclosure. In any of the foregoing embodiments, the individual may be a human individual. An individual can be male or female and can be any age-appropriate individual, including infants, juveniles, youth, adults and old age.

It is believed that multiple criteria lead to a higher risk of severe symptoms or death associated with SARS CoV-2 infection. These include, but are not limited to, age, occupation, general health, pre-existing health conditions and lifestyle habits. In some embodiments, an individual treated in accordance with the present disclosure comprises one or more risk factors.

In certain embodiments, human subjects treated in accordance with the present disclosure are infants, children, adolescents, middle-aged and elderly individuals. In certain embodiments, the human subject treated in accordance with the present disclosure is less than 1 year old, or 1 to 5 years old, or between 5 and 125 years old (eg, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115 or 125 years of age, including any and all ages in between). In certain embodiments, the human subject treated in accordance with the present disclosure is 0-19 years old, 20-44 years old, 45-54 years old, 55-64 years old, 65-74 years old, 75-84 years old, or 85 years old, or older age. It is believed that middle-aged individuals, and especially older individuals, are at particular risk. In certain embodiments, the human subject is 45-54 years old, 55-64 years old, 65-74 years old, 75-84 years old or 85 years old, or older. In some embodiments, the human subject is biologically male. In some embodiments, the human subject is biologically female.

In certain embodiments, the human subject treated in accordance with the present disclosure is a resident of a nursing home or long-term care facility; is a hospice care worker; is a health care provider or health care worker; be a family member or other close contact of an individual diagnosed with or suspected of having SARS-CoV-2 infection; be overweight or clinically obese; be or have been a smoker; have or have had chronic obstructive pulmonary disease ( COPD); is asthmatic (eg, with moderate-to-severe asthma); has an autoimmune disease or condition (eg, diabetes); and/or has a compromised or depleted immune system (eg, due to AIDS/ HIV infection, cancer such as blood cancer, lymphodepleting therapy such as chemotherapy, bone marrow or organ transplantation, or genetic immune conditions); having chronic liver disease; having cardiovascular disease; having lung or heart disease; with others Work or otherwise come into close contact, such as in a factory, transportation center, hospital setting, or the like.

In certain embodiments, an individual treated in accordance with the present disclosure has received a vaccine against SARS-CoV-2, and the vaccine is determined by clinical diagnosis or scientific or regulatory consensus, such as by post-vaccination infection or symptoms in the individual is invalid (ie, at least partially or completely invalid).

In certain embodiments, treatment is administered as prophylaxis during exposure. In certain embodiments, treatment is administered to individuals with mild to moderate disease, who can be administered in an outpatient setting. In certain embodiments, treatment is administered to individuals with moderate to severe disease, such as requiring hospitalization.

Typical routes of administration of the compositions disclosed herein include, but are not limited to, oral, topical, transdermal, inhalation, parenteral, sublingual, buccal, rectal, vaginal, and intranasal. As used herein, the term "parenteral" includes subcutaneous injection, intravenous, intramuscular, intrasternal injection or infusion techniques. In certain embodiments, administering comprises administering by a route selected from the group consisting of oral, intravenous, parenteral, intragastric, intrapleural, intrapulmonary, intrarectal, intradermal, intraperitoneal, intratumoral , subcutaneous, topical, percutaneous, intracisternal, intrathecal, intranasal and intramuscular. In certain embodiments, the method comprises orally administering the antibody, antigen-binding fragment, polynucleotide, vector, host cell or composition to an individual.

Pharmaceutical compositions according to certain embodiments of the present invention are formulated such that the active ingredient contained therein is bioavailable upon administration of the composition to a patient. The composition to be administered to an individual or patient can be in the form of one or more dosage units, wherein, for example, a lozenge can be a single dosage unit, and the antibody or antigen-binding containers described herein in aerosol form can hold multiple dosage unit. Actual methods of preparing such dosage forms are known or will be apparent to those skilled in the art; see, for example, Remington: The Science and Practice of Pharmacy, 20th Ed. (Philadelphia College of Pharmacy and Science, 2000) . The composition to be administered will in any event contain an effective amount of an antibody or antigen-binding fragment, polynucleotide, vector, host cell or composition of the disclosure to treat a disease of interest or a composition in accordance with the teachings herein. Symptoms.

The composition can be in solid or liquid form. In some embodiments, the carrier is a particle, such that the composition is in the form of a tablet or powder, for example. The carrier or carriers can be liquids and the compositions are, for example, oral oils, injectable liquids, or aerosols suitable for administration, eg, by inhalation. When intended for oral administration, the pharmaceutical composition is preferably in solid or liquid form, with semi-solid, semi-liquid, suspension, and gel forms included within forms considered herein to be solid or liquid.

As a solid composition for oral administration, the pharmaceutical composition can be formulated into powders, granules, compressed tablets, pills, capsules, chewable tablets, powder tablets or the like. Such solid compositions will generally contain one or more inert diluents or edible carriers. Additionally, one or more of the following may be present: binders such as carboxymethyl cellulose, ethyl cellulose, microcrystalline cellulose, tragacanth or gelatin; excipients such as starch, lactose or dextrin; Disintegrants such as alginic acid, sodium alginate, sodium starch glycolate (Primogel), corn starch and the like; lubricants such as magnesium stearate or hydrogenated vegetable oils (Sterotex); slip agents such as colloidal dimethacrylate Silicon oxide; sweeteners such as sucrose or saccharin; flavoring agents such as peppermint, methyl salicylate, or citrus flavoring; and coloring agents. When the composition is in the form of a capsule (eg, a gelatin capsule), it may contain, in addition to materials of the above type, a liquid carrier such as polyethylene glycol or an oil.

The composition may be in liquid form, such as an elixir, syrup, solution, emulsion or suspension. Liquids can be used for oral administration or for delivery by injection, to name two examples. When intended for oral administration, preferred compositions contain, in addition to the compounds of the present invention, one or more of sweeteners, preservatives, dyes/colorants and flavor enhancers. In compositions intended for administration by injection, one or more of surfactants, preservatives, wetting agents, dispersing agents, suspending agents, buffers, stabilizers and isotonic agents may be included.

Liquid pharmaceutical compositions, whether in solution, suspension, or other similar form, may include one or more of the following adjuvants: sterile diluents, such as water for injection, saline solution, preferably saline, Ringer's Ringer's solution, isotonic sodium chloride, fixed oils such as synthetic mono- or diglycerides, polyethylene glycol, glycerol, propylene glycol or other solvents which can act as a solvent or suspending medium; Antibacterial agents such as benzyl alcohol or methylparaben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as EDTA; buffers such as acetate, citrate or phosphate; and tonicity modifiers such as sodium chloride or dextrose. Parenteral preparations can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. Physiological saline is the preferred adjuvant. Injectable pharmaceutical compositions are preferably sterile.

Liquid compositions intended for parenteral or oral administration should contain an antibody or antigen-binding fragment as disclosed herein in an amount such that a suitable dosage will be obtained. Typically, this amount is at least 0.01% of the antibody or antigen-binding fragment in the composition. When intended for oral administration, this amount can vary between 0.1% and about 70% by weight of the composition. Certain oral pharmaceutical compositions contain between about 4% and about 75% antibody or antigen-binding fragment. In certain embodiments, pharmaceutical compositions and formulations according to the present invention are prepared such that a parenteral dosage unit contains between 0.01 and 10% by weight of the antibody or antigen-binding fragment prior to dilution.

The composition may be intended for topical administration, in which case the vehicle may suitably comprise a solution, emulsion, ointment or gel base. For example, the base may comprise one or more of the following: paraffin grease, wool wax, polyethylene glycol, beeswax, mineral oil, diluents such as water and alcohol, and emulsifiers and stabilizers. Thickening agents can be present in the composition for topical administration. If intended for transdermal administration, the composition may comprise a transdermal patch or an iontophoresis device. The pharmaceutical composition may be intended for rectal administration, eg, in the form of a suppository that will melt in the rectum and release the drug. Compositions for rectal administration may contain an oily base as a suitable non-irritating excipient. Such bases include, but are not limited to, wool wax, cocoa butter, and polyethylene glycols.

The composition can include various materials that alter the physical form of the solid or liquid dosage unit. For example, the composition may include a material that forms a coating around the active ingredient. The material forming the coating shell is generally inert and can be selected from, for example, sugar, shellac and other enteric coating agents. Alternatively, the active ingredient may be enclosed in gelatin capsules. The composition, in solid or liquid form, can include an agent that binds to the antibody or antigen-binding fragment of the present disclosure, and thereby aids in delivery of the compound. Suitable agents that can exert this ability include monoclonal or polyclonal antibodies, one or more proteins, or liposomes. The composition may consist essentially of dosage units which can be administered in the form of aerosols. The term aerosol is used to denote a variety of systems ranging from those systems of colloidal nature to those consisting of pressurized packaging. Delivery can be by liquefied or compressed gas or by a suitable pump system that dispenses the active ingredient. Aerosols can be delivered in monophasic, biphasic or triphasic systems to deliver active ingredients. Delivery of an aerosol includes the necessary container, activator, valve, sub-container, and the like, which together can form a kit. Those skilled in the art can generally determine the preferred aerosol without undue experimentation.

It is to be understood that the compositions of the present disclosure also encompass carrier molecules (eg, lipid nanoparticles, nanoscale delivery platforms, and the like) for the polynucleotides described herein.

Pharmaceutical compositions can be prepared by methods well known in the medical art. For example, a composition intended to be administered by injection may be prepared by incorporating an antibody, antigen-binding fragment or antibody conjugate thereof as described herein, and optionally, in a salt, buffer, and/or stabilizer. One or more of the compositions are prepared by combining with sterile distilled water to form a solution. Surfactants can be added to facilitate the formation of a homogeneous solution or suspension. Surfactants are compounds that non-covalently interact with peptide compositions to facilitate solubilization or uniform suspension of antibodies or antigen-binding fragments thereof in aqueous delivery systems.

In general, appropriate dosages and treatment regimens provide a dose sufficient to provide therapeutic and/or prophylactic benefits (such as those described herein, including improved clinical outcomes (eg, reduced frequency, duration, or severity of diarrhea or associated dehydration or inflammation, or longer disease-free and/or overall survival, or reduced severity of symptoms) of the composition. For prophylactic use, the dosage should be sufficient to prevent, delay the onset, or reduce the severity of the disease associated with the disease or disorder. The prophylactic benefit of the compositions administered according to the methods described herein can be obtained by conducting preclinical (including in vitro and in vivo animal studies) and clinical studies, and by analysis of the self by appropriate statistical, biological and clinical methods and techniques. It is determined from the data obtained that it can be easily practiced by those skilled in the art.

The composition is administered in an effective amount (eg, to treat a coronavirus infection), which will vary depending on a number of factors including: the activity of the particular compound employed; the metabolic stability and duration of action of the compound; Age, weight, general health, gender, and diet; mode and time of administration; rate of excretion; drug combination; severity of particular disorder or condition; and individuals undergoing therapy. In certain embodiments, following administration of therapy in accordance with the formulations and methods of the present disclosure, test subjects will exhibit one or more associated with a disease or disorder compared to placebo-treated or other suitable control subjects About 10% up to about 99% reduction in symptoms.

Typically, a therapeutically effective daily dose of antibody or antigen-binding fragment is (for a 70 kg mammal) about 0.001 mg/kg (ie, 0.07 mg) to about 100 mg/kg (ie, 7.0 g); preferably therapeutically effective The dose is (for a 70 kg mammal) about 0.01 mg/kg (ie, 0.7 mg) to about 50 mg/kg (ie, 3.5 g); a more preferred therapeutically effective dose is (for a 70 kg mammal) about 1 mg/kg (ie, 70 mg) to about 25 mg/kg (ie, 1.75 g). For the polynucleotides, vectors, host cells, and related compositions of the present disclosure, the therapeutically effective dose can be different from the therapeutically effective dose of the antibody or antigen-binding fragment.

In certain embodiments, the method comprises administering the antibody, antigen-binding fragment, polynucleotide, vector, host cell or composition to the subject 2, 3, 4, 5, 6, 7, 8, 9, 10 times or more times.

In certain embodiments, the method comprises administering the antibody, antigen-binding fragment, or composition multiple times to the subject, wherein the second or consecutive administrations are about 6, about 7, About 8, about 9, about 10, about 11, about 12, about 24, about 48, about 74, about 96 hours or more.

In certain embodiments, the methods comprise administering the antibody, antigen-binding fragment, polynucleotide, vector, host cell or composition at least once prior to infection of the individual by SARS-CoV-2.

Compositions comprising antibodies, antigen-binding fragments, polynucleotides, vectors, host cells, or compositions of the present disclosure may also be administered concurrently with, prior to, or subsequent to administration of one or more other therapeutic agents. Such combination therapy may include administration of a single pharmaceutical dosage form formulation containing a compound of the present invention and one or more additional active agents, as well as administration of a composition comprising an antibody or antigen-binding fragment of the present disclosure, with each active agent in its In the form of a separate dosage formulation on its own. For example, an antibody or antigen-binding fragment thereof and other active agents as described herein can be administered to a patient together in a single oral dosage composition, such as a lozenge or capsule, or each agent administered as a separate oral dosage formulation . Similarly, antibodies or antigen-binding fragments as described herein and other active agents can be administered to an individual together in a single parenteral dosage composition, such as in physiological saline solution or other physiologically acceptable solution, or Each agent is administered as a separate parenteral dosage formulation. When separate dosage formulations are used, the composition comprising the antibody or antigen-binding fragment and one or more additional active agents may be administered substantially simultaneously, that is, concurrently, or at separately staggered times, that is, sequentially and in any Sequential administration; combination therapy is understood to include all such regimens.

In certain embodiments, there is provided a combination therapy comprising one or more anti-Sabe coronavirus antibodies of the present disclosure, such as an anti-SARS-CoV-2 antibody (or one or more nucleic acids, host cells, vectors or composition) and one or more anti-inflammatory agents and/or one or more antiviral agents. In certain embodiments, the one or more anti-inflammatory agents comprise a corticosteroid, such as dexamethasone, prisone, or an analog thereof. In some embodiments, the one or more anti-inflammatory agents comprise a cytokine antagonist, such as that binds to IL6 (such as srtuximab), or binds to IL-6R (such as tocilizumab), or binds To IL-1β, IL-7, IL-8, IL-9, IL-10, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1A, MIP1-B , PDGR, TNF-α or VEGF antibody. In some embodiments, anti-inflammatory agents such as rulitinib and/or anakinra are used. In some embodiments, the one or more antiviral agents comprise nucleotide analogs or nucleotide mimic prodrugs, such as remdesivir, sofosbuvir, acyclovir, and zidovudine (zidovudine). In particular embodiments, the antiviral agent comprises lopinavir, ritonavir, favipiravir, or any combination thereof. In some embodiments, the combination therapy comprises lelonimab. Anti-inflammatory agents used in combination therapy of the present disclosure also include non-steroidal anti-inflammatory drugs (NSAIDS). It will be appreciated that in such combination therapy, one or more antibodies (or one or more nucleic acids, host cells, vectors or compositions) and one or more anti-inflammatory and/or one or more antiviral agents may Administered in any order and in any order or together.

In some embodiments, the antibody (or one or more nucleic acids, host cells, vectors, or compositions) is administered to an individual who has previously received one or more anti-inflammatory agents and/or one or more antiviral agents. In some embodiments, one or more anti-inflammatory agents and/or one or more antiviral agents are administered to an individual who has previously received the antibody (or one or more nucleic acids, host cells, vectors, or compositions).

In certain embodiments, there is provided a combination therapy comprising two or more anti-SARS-CoV-2 antibodies, either or both of which may be antibodies of the disclosure. A method may comprise administering the first antibody to an individual who has received the second antibody, or may comprise administering two or more antibodies together. For example, in certain embodiments, there is provided a method comprising administering to an individual (a) a first antibody or antigen-binding fragment, when the individual has received a second antibody or antigen-binding fragment; (b) a second antibody or antigen-binding fragment; An antibody or antigen-binding fragment, when the individual has received the first antibody or antigen-binding fragment; or (c) the first antibody or antigen-binding fragment, and the second antibody or antigen-binding fragment.

In some embodiments, any of the antibodies disclosed herein can be used in a method of treating or preventing SARS-CoV-2 infection, wherein the method further comprises using an antibody or antigen-binding fragment comprising: (i) as SEQ ID, respectively The CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in NO.: 343-345 and 347-349; or (ii) as set forth in SEQ ID NO.: 140-142 and 144-146, respectively The CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences as set forth; or (iii) the VH and VL amino acid sequences as set forth in SEQ ID NO.: 342 and 346, respectively; or (iv) as set forth in SEQ ID NO.: 342 and 346, respectively VH and VL amino acid sequences set forth in SEQ ID NO.: 139 and 143.

In a related aspect, uses of the disclosed antibodies, antigen-binding fragments, vectors, host cells, and compositions are provided.

In certain embodiments, antibodies, antigen-binding fragments, polynucleotides, vectors, host cells or compositions are provided for use in a method of treating a SARS-CoV-2 infection in an individual.

In certain embodiments, antibodies, antigen-binding fragments or compositions are provided for use in a method of making or preparing a medicament for the treatment of SARS-CoV-2 infection in an individual.

The present disclosure also provides the following examples:

Embodiment 1. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the The light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein: (i) the CDRH1 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NO.: 400, 23, 33, 43, 53, 63, 75, 85, 97, 107, 120, 130, 140, 147, 160, 170, 174, 183, 190, 199, 209, 219, 229, 241, 255, 265, 275, 285, 299, 313, 323, 333, 370, 380, 390, 410, or including one , sequence variants with two or three acid substitutions, one or more of which are optionally conservative substitutions and/or substitutions for germline encoded amino acids; (ii) the CDRH2 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NO.: 401, 24, 34, 44, 54, 64, 76, 86, 98, 108, 121, 131, 141, 148, 151, 161, 171, 184, 200, 210, 220, 230, 242, 256, 266, 276, 286, 300, 314, 324, 334, 352, 360, 362, 364, 366, 371, 381, 391, 411, 421, 431, 436, 446, 456, 466, 476, 486, 496, 506, 516, 526, 536, 546, 556, 566, 576, 586, 596, 606, 616, 625, 632, 635, 637, 639, 641, 643, 645, 647, 649, 651, 653, 655, 657, 659, 661, 663, 665, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685 and 694, or sequence variants thereof comprising one, two or three amino acid substitutions, one or more of which are optionally conserved substitutions and/or for germline Substitution of the encoded amino acid; (iii) the CDRH3 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NO.: 766, 25, 35, 45, 55, 65, 77, 87, 99, 109, 122, 132, 142, 149, 162, 164, 165, 172, 176, 177, 179, 180, 185, 187, 188, 201, 211, 221, 231, 243, 257, 267, 277, 287, 301, 315, 325, 335, 354, 372, 382, 392, 412, 422, 432, 437, 447, 457, 467, 477, 487, 497, 507, 517, 527, 537, 547, 557, 567, 577, 587, 597, 607, 617, 627, 633, 695, 751, 753, 755, 757, 760, 763, 765 and 402, or sequence variants thereof comprising one, two or three amino acid substitutions, such substitutions One or more of these are optionally conservative substitutions and/or substitutions to germline encoded amino acids; (iv) the CDRL1 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NO.: 404, 27, 37, 47, 57, 67, 79, 89, 101, 111, 124, 134, 144, 152, 155, 156, 158, 159, 166, 181, 192, 203, 213, 223, 233, 245, 259, 269, 279, 289, 303, 317, 327, 337, 356, 374, 384, 394, 414, 424, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 687 and 697, or sequence variants thereof comprising one, two or three amino acid substitutions, one or more of which are optionally conservative substitutions and/or substitutions for germline encoded amino acids; (v) the CDRL2 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NO.: 405, 28, 38, 48, 58, 68, 80, 90, 102, 112, 125, 135, 145, 153, 167, 182, 193, 204, 214, 224, 234, 246, 260, 270, 280, 290, 304, 318, 328, 338, 375, 385, 395, 415, 425, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 688 and 698, or including one, two or three Sequence variants of amino acid substitutions, one or more of which are optionally conservative substitutions and/or substitutions for germline-encoded amino acids; and/or (vi) the CDRL3 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NO.: 406, 29, 39, 49, 59, 69, 81, 91, 103, 113, 126, 136, 146, 169, 195, 197, 205, 215, 225, 235, 247, 261, 271, 281, 291, 305, 319, 329, 339, 358, 376, 386, 396, 416, 426, 441, 451, 461, 471, 481, 491, 501, 511, 521, 531, 541, 551, 561, 571, 581, 591, 601, 611, 621, 689, 699, 745 and 747, or including one, two Sequence variants of one or three amino acid substitutions, one or more of which are optionally conservative substitutions and/or substitutions for germline encoded amino acids, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 2. The antibody or antigen-binding fragment of Embodiment 1, which is capable of neutralizing SARS-CoV-2 infection in an in vitro infection model and/or an in vivo animal infection model and/or in humans.

Embodiment 3. The antibody or antigen-binding fragment of any one of embodiments 1 to 2, comprising the following CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences: (i) are respectively SEQ ID NO. : 400, 401, 766 and 404-406; (ii) are respectively SEQ ID NO.: 400-402 and 404-406; (iii) are respectively SEQ ID NO.: 43-45 and 47-49; (iv) respectively SEQ ID NO.: 53-55 and 57-59; (v) respectively SEQ ID NO.: 63-65 and 67-69; (vi) respectively SEQ ID NO.: 75-77 and 79-81 (vii) are respectively SEQ ID NO.: 85-87 and 89-91; (viii) are respectively SEQ ID NO.: 97-99 and 101-103; (ix) are respectively SEQ ID NO.: 107-109 and 111-113; (x) are respectively SEQ ID NO.: 120-122 and 124-126; (xi) are respectively SEQ ID NO.: 130-132 and 134-136; (xii) are respectively SEQ ID NO. : any one of 23 or 147, 24, 148 or 151, 25 or 149, 27, 152, 155, 156, 158 or 159, 28 or 153, and any one of 29; (xiii) are SEQ respectively ID NO.: 43 or 160, 44 or 161, any one of 45, 162, 164 or 165, 47 or 166, 48 or 167, and 49 or 169; (xiv) are SEQ ID NO.: 130, any one of 170 or 174, 130, 131, 132, 134 or 181, 135 or 182, and 136; (xv) is any one of SEQ ID NO.: 53, 183 or 190, 54 or 184, respectively , any of 55, 185, 187 or 188, any of 57 or 192, 58 or 193, and any of 59, 195 or 197; (xvi) are SEQ ID NO.: 199, respectively -201 and 203-205; (xvii) respectively SEQ ID NO.: 209-211 and 213-215; (xviii) respectively SEQ ID NO.: 219-221 and 223-225; (xix) respectively SEQ ID NO.: 229-231 and 233-235; (xx) are respectively SEQ ID NO.: 241-243 and 245-247; (xxi) are respectively SEQ ID NO.: 255-257 and 259-261; (xxii) SEQ ID NO.: 265-267 and 269-271 respectively; (xxiii) SEQ ID NO.: 275-277 and 279-281 respectively; (xxiv) SEQ ID NO.: 285-287 and 289-291 respectively (xxv) are respectively SEQ ID NO.: 299-301 and 303-305; (xxvi) are respectively SEQ ID NO.: 313-315 and 317-319; (xxvii) are respectively SEQ ID NO.: 323-325 and 327-329; (xxviii) are respectively SEQ ID NO.: 333-335 and 337-339; (xxix) are respectively SEQ ID NO.: 229, 230 or 352, 231 or 354, and 233 or 356, 234, and 235 or 358; (xxx) are respectively any one of SEQ ID NO.: 313, 314, 360, 362, 364 or 366, 315 and 317-319; (xxxi) are respectively SEQ ID NO.: 370- 372 and 374-376; (xxxii) SEQ ID NO.: 380-382 and 384-386, respectively; (xxxiii) SEQ ID NO.: 390-392 and 394-396, respectively; (xxxiv) 23-25 and 27 -29; (xxxv) are respectively SEQ ID NO.: 410-412 and 414-416; (xxxvi) are respectively SEQ ID NO.: 420-422 and 424-426; (xxxvii) are respectively SEQ ID NO.: 435 -437 and 439-441; (xxxviii) are SEQ ID NO.: 445-447 and 449-451, respectively; (xxxix) are SEQ ID NO.: 455-457 and 459-461, respectively; (xxxx) are SEQ ID NO.: 455-457 and 459-461, respectively NO.: 465-467 and 469-471; (xxxxi) are respectively SEQ ID NO.: 475-477 and 479-481; (xxxxii) are respectively SEQ ID NO.: 485-487 and 489-491; (xxxxiii) SEQ ID NO.: 494-497 and 499-501 respectively; (xxxxiv) SEQ ID NO.: 505-507 and 509-511 respectively; (xxxxv) SEQ ID NO.: 515-517 and 519-521 respectively (xxxxvi) are respectively SEQ ID NO.: 525-527 and 529-531; (xxxxvii) are respectively SEQ ID NO.: 5 35-537 and 539-541; (xxxxviii) are SEQ ID NO.: 545-547 and 549-551 respectively; (xxxix) are SEQ ID NO.: 555-557 and 559-561 respectively; (xxxxx) are SEQ ID NO.: 555-557 and 559-561 respectively ID NO.: 565-567 and 569-571; (xxxxxi) are respectively SEQ ID NO.: 575-577 and 579-581; (xxxxxii) are respectively SEQ ID NO.: 585, 586 or 625, 587 or 627, and 589-591; (xxxxxiii) are respectively SEQ ID NO.: 595-597 and 599-601; (xxxxxiv) are respectively SEQ ID NO.: 605-607 and 609-611; (xxxxxv) are respectively SEQ ID NO. : 615-617 and 619-621; (xxxxxvi) are respectively SEQ ID NO.: 631, 632 or 635 or 637 or 639 or 641 or 643 or 645 or 647 or 649 or 651 or 653 or 655 or 657 or 659 or 661 or 663 or 665 or 667 or 669 or 671 or 673 or 675 or 677 or 679 or 681 or 683 or 685, 633 and 697-699; (xxxxxvii) are SEQ ID NO.: 693-695 and 697-699, respectively; ( xxxxxviii) are SEQ ID NO.: 400, 401, and any one of 751, 753, 755, 757 or 760, respectively, and any one of 404, 405, and 745 or 747; (xxxxxxix) are SEQ ID NOs, respectively ID NO.: 585, 586, and 762 or 764, and 589-591; (xxxxxxx) are SEQ ID NO.: 33-35 and 37-39, respectively; or (xxxxxxxi) are SEQ ID NO.: 400; 401, respectively 766; 404; 405 or a variant of 405 comprising one, two or three amino acid substitutions, wherein each of the one, two or three amino acid substitutions is optionally a conserved amino group and 406. acid substitution;

Embodiment 4. An antibody or antigen-binding fragment thereof comprising CDRH1, CDRH2 and CDRH3 of the VH amino acid sequence set forth in SEQ ID NO.:399, and the VL amino group set forth in SEQ ID NO.:738 CDRL1, CDRL2 or variant of CDRL2 comprising one, two or three amino acid substitutions of acid sequence, wherein each of the one, two or three amino acid substitutions is optionally a conserved amino group acid substitution; and CDRL3, wherein the CDRs are according to IMGT, And wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion. Embodiment 5. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a complementarity determining region (CDR) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in: (a) SEQ respectively ID NO.: 400, 401, 766, 404, 405 and 406; (b) SEQ ID NO.: 400, 401, 769, 404, 405 and 406 respectively; (c) SEQ ID NO.: 400, 401, 770, 404, 405 and 406; (d) are respectively SEQ ID NO.: 400, 401, 771, 404, 405 and 406; (e) are respectively SEQ ID NO.: 400, 401, 772, 404, 405 and 406; (f) are SEQ ID NO.: 400, 401, 773, 404, 405 and 406, respectively; (g) are SEQ ID NO.: 400, 401, 766, 404, 405 and 745, respectively; (h) ) are respectively SEQ ID NO.: 400, 401, 769, 404, 405 and 745; (i) are respectively SEQ ID NO.: 400, 401, 770, 404, 405 and 745; (j) are respectively SEQ ID NO. .: 400, 401, 771, 404, 405 and 745; (k) respectively SEQ ID NO.: 400, 401, 772, 404, 405 and 745; (l) respectively SEQ ID NO.: 400, 401, 773, 405, 405 and 745; (m) are SEQ ID NO.: 400, 401, 766, 404, 405 and 747, respectively; (n) are SEQ ID NO.: 400, 401, 769, 404, 405 and 747; (o) are SEQ ID NO.: 400, 401, 770, 404, 405 and 747, respectively; (p) are SEQ ID NO.: 400, 401, 771, 404, 405 and 747, respectively; (q) are respectively is SEQ ID NO.: 400, 401, 772, 404, 405 and 747; or (r) is SEQ ID NO.: 400, 401, 773, 404, 405 and 747, respectively, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 6. The antibody or antigen-binding fragment thereof of embodiment 5, comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in: (a) SEQ ID NOs, respectively .:400, 401, 766, 404, 405 and 406.

Embodiment 7. The antibody or antigen-binding fragment of any one of embodiments 4-6, comprising the amino acid sequence set forth in: (a) SEQ ID NO.: 400, 401, 402, 404, 405 and 406; (b) SEQ ID NO.: 400, 401, 751, 404, 405 and 406; (c) SEQ ID NO.: 400, 401, 753, 404, 405 and 406; (d) SEQ ID NO. : 400, 401, 755, 404, 405 and 406; (e) SEQ ID NO.: 400, 401, 757, 404, 405 and 406; (f) SEQ ID NO.: 400, 401, 760, 404, 405 and 406; (g) SEQ ID NO.: 400, 401, 402, 404, 405 and 745; (h) SEQ ID NO.: 400, 401, 751, 404, 405 and 745; (i) SEQ ID NO. : 400, 401, 753, 404, 405 and 745; (j) SEQ ID NO.: 400, 401, 755, 404, 405 and 745; (k) SEQ ID NO.: 400, 401, 757, 404, 405 and 745; (l) SEQ ID NO.: 400, 401, 760, 404, 405 and 745; (m) SEQ ID NO.: 400, 401, 402, 404, 405 and 747; (n) SEQ ID NO. : 400, 401, 751, 404, 405 and 747; (o) SEQ ID NO.: 400, 401, 753, 404, 405 and 747; (p) SEQ ID NO.: 400, 401, 755, 404, 405 and 747; (q) SEQ ID NO.: 400, 401, 757, 404, 405 and 747; or (r) SEQ ID NO.: 400, 401, 760, 404, 405 and 747.

Embodiment 8. The antibody or antigen-binding fragment of any one of embodiments 4-7, comprising the amino acid sequence set forth in SEQ ID NO.: 400, the amino acid sequence set forth in SEQ ID NO.: 401 in VH and the amino acid sequence set forth in SEQ ID NO.:402, and the amino acid sequence set forth in SEQ ID NO.:404, set forth in SEQ ID NO.:405 in VL and the amino acid sequence set forth in SEQ ID NO.:406.

Embodiment 9. A kind of antibody or its antigen-binding fragment, it comprises heavy chain variable domain (VH) and light chain variable domain (VL), this heavy chain variable domain (VH) comprises complementarity determining region (CDR) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in: SEQ ID NO. : 525, 526, 527, 529, 530 and 531, And wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion. Embodiment 10. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a complementarity determining region (CDR) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in: SEQ ID NO. : 585, 586 or 625, 587 or 627, 589, 590 and 591, And wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 11. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising complementarity determining regions (CDRs) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in: SEQ ID NO. : 229, 230, 231, 233, 234 and 235, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 12. The antibody or antigen-binding fragment of any one of embodiments 1-11, wherein: (i) the VH comprises at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences or consist of: SEQ ID NO.: 399, 22, 32, 42, 52, 62, 72, 74, 84, 96, 106, 119, 129, 139, 150, 163, 173, 175, 178, 186, 189, 191, 198, 208, 218, 228, 240, 254, 264, 274, 284, 298, 312, 322, 332, 350, 351, 353, 359, 361, 363, 365, 367, 368, 369, 379, 389, 409, 419, 429, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 626, 628, 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 692, 740, 741, 742, 743, 748, 749, 750, 752, 754, 756, 758, 759, 761, 762 and 764, wherein the change is optionally limited to one or more framework regions and/or the change comprises a germline encoded amino acid one or more substitutions; and/or (ii) the VL comprises at least 85% (eg, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences or consist of: SEQ ID NO.: 738, 26, 36, 46, 56, 66, 78, 88, 94, 100, 110, 123, 133, 143, 154, 157, 168, 194, 196, 202, 212, 222, 232, 238, 244, 250, 252, 258, 268, 278, 288, 294, 296, 302, 308, 310, 316, 326, 336, 355, 357, 373, 383, 393, 403, 413, 423, 438, 448, 458, 468, 478, 488, 498, 508, 518, 528, 538, 548, 558, 568, 578, 588, 598, 608, 618, 686, 696, 744 and 746, wherein the variation is optionally limited to one or more framework regions and/or the variation Contains one or more substitutions to the germline encoded amino acid.

Embodiment 13. The antibody or antigen-binding fragment of any one of embodiments 1-12, wherein the VH comprises an amine group that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO.:399 The VL comprises or consists of an amino acid sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738.

Embodiment 14. The antibody or antigen-binding fragment of any one of embodiments 1-13, wherein the VH comprises an amine group that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO.:399 The VL comprises or consists of an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738.

Embodiment 15. The antibody or antigen-binding fragment of any one of embodiments 1-14, wherein the VH comprises an amine group that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO.:399 The VL comprises or consists of an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738.

Embodiment 16. The antibody or antigen-binding fragment of any one of embodiments 1-15, wherein the VH comprises an amine group that is at least 97% identical to the amino acid sequence set forth in SEQ ID NO.:399 an acid sequence, and the VL comprises or consists of an amino acid sequence that is at least 97% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738.

Embodiment 17. The antibody or antigen-binding fragment of any one of technical solutions 1-16, wherein the VH comprises an amino group having at least 99% identity with the amino acid sequence set forth in SEQ ID NO.:399 The VL comprises or consists of an amino acid sequence that is at least 99% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738.

Embodiment 18. The antibody or antigen-binding fragment of any one of embodiments 1-12, wherein the VH and the VL are at least 85% identical to the amino acid sequences set forth below (eg, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%): (i) are SEQ ID NO.: 524 and 528, respectively; (ii) are SEQ ID NO.: 584 or 624 or 626 or 628 and 588, respectively; (iii) SEQ ID NO.: 228 or 740 or 741 or 742 or 743 and 232, respectively; or (iv) are SEQ ID NO.: 228 or 740 or 741 or 742 or 743 and 238, respectively.

Embodiment 19. as the antibody or antigen-binding fragment of any one of embodiment 1-18, wherein this VH comprises or consists of any VH amino acid sequence set forth in table 2, and wherein this VL comprises in table 2 Any VL amino acid sequence set forth or consists of, wherein optionally, the VH and the VL comprise or consist of the amino acid sequences according to: (i) SEQ ID NO.: 399 and 403 or 738; (ii) respectively SEQ ID NO.: 32 and 36; (iii) respectively SEQ ID NO.: 42 and 46; (iv) respectively SEQ ID NO.: 52 and 56; (v) respectively are SEQ ID NO.: 62 and 66; (vi) are respectively SEQ ID NO.: 72 and 66; (vii) are respectively SEQ ID NO.: 74 and 78; (viii) are respectively SEQ ID NO.: 84 and 88; (ix) are SEQ ID NO.: 84 and 88, respectively; (x) respectively SEQ ID NO.: 96 and 100; (xi) respectively SEQ ID NO.: 106 and 110; (xii) respectively SEQ ID NO.: 119 and 123; or (xiii) respectively SEQ ID NO.: 129 and 133; (xiv) are respectively SEQ ID NO.: 22 or 150 and 26, 154 or 157; (xv) are respectively SEQ ID NO.: 42 or 163 and 46 or 168; (xvi) are respectively Any one of SEQ ID NO.: 129, 173, 175 or 178 and 133; (xvii) is any one of SEQ ID NO.: 52, 186, 189 or 191 and any one of 56, 194 or 196, respectively Any one; (xviii) are respectively SEQ ID NO.: 198 and 202; (xix) are respectively SEQ ID NO.: 208 and 212; (xx) are respectively SEQ ID NO.: 218 and 222; (xxi) are respectively are SEQ ID NO.: 228 and 232 or 238; (xxii) are SEQ ID NO.: 240, and any one of 244, 250 or 252, respectively; (xxiii) are SEQ ID NO.: 254 and 258, respectively; (xxiv) are SEQ ID NO.: 264 and 258, respectively 268; (xxv) are SEQ ID NO.: 274 and 278, respectively; or (xxvi) is SEQ ID NO.: 284, and any one of 288, 294, or 296, respectively; (xxvii) is SEQ ID NO.: 298, and any one of 302, 308, or 310, respectively; (xxviii) ) are respectively SEQ ID NO.: 312 and 316; (xxix) are respectively SEQ ID NO.: 322 and 326; (xxx) are respectively SEQ ID NO.: 332 and 336; (xxxi) are respectively SEQ ID NO.: 228, 350, 351 or 353 and any one of 232, 238, 355 or 357; (xxxii) respectively SEQ ID NO.: any one of 312, 359, 361, 363, 365, 367 or 368 and 316; (xxxiii) are respectively SEQ ID NO.: 369 and 373; (xxxiv) are respectively SEQ ID NO.: 379 and 383; (xxxv) are respectively SEQ ID NO.: 389 and 393; (xxxvi) are respectively SEQ ID NO.: 389 and 393 ID NO.: 22 and 26; (xxxvii) are respectively SEQ ID NO.: 409 and 413; (xxxviii) are respectively SEQ ID NO.: 419 and 423; (xxxix) are respectively SEQ ID NO.: 434 and 438; (xxxx) are respectively SEQ ID NO.: 444 and 448; (xxxxi) are respectively SEQ ID NO.: 454 and 458; (xxxxii) are respectively SEQ ID NO.: 464 and 468; (xxxxiii) are respectively SEQ ID NO. .: 474 and 478; (xxxxiv) are respectively SEQ ID NO.: 484 and 488; (xxxxv) are respectively SEQ ID NO.: 494 and 498; (xxxxvi) are respectively SEQ ID NO.: 504 and 508; (xxxxvii ) are respectively SEQ ID NO.: 514 and 518; (xxxxviii) are respectively SEQ ID NO.: 524 and 528; (xxxix) are respectively SEQ ID NO.: 534 and 538; (xxxxx) are respectively SEQ ID NO.: 544 and 548; (xxxxxxi) are respectively SEQ ID NO.: 554 and 558; (xxxxxii) are respectively SEQ ID NO.: 564 and 568; (xxxxxiii) are respectively SEQ ID NO.: 574 and 578; (xxxxxiv) are respectively are SEQ ID NO.: 584 and 588; (xxxxxv) are SEQ ID NO.: 594 and 59, respectively 8; (xxxxxvi) are respectively SEQ ID NO.: 604 and 608; (xxxxxvii) are respectively SEQ ID NO.: 614 and 618; (xxxxxviii) are respectively SEQ ID NO.: 624, 626 or 628 and 588; (xxxxxix) are respectively is SEQ ID NO.: 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682 or 684 and 686; (xxxxxx) are SEQ ID NO.: 692 and 696, respectively; (xxxxxxi) are any of SEQ ID NO.: 740-743 and 238, respectively; (xxxxxxii) are respectively SEQ ID NO.: any one of 399, 748, 749, 750, 752, 754, 756, 758, 759 and 761 and any one of 403, 744 and 746; or (xxxxxxiii) are respectively SEQ ID NO. ID NO.: 762 or 764 and 588.

Embodiment 20. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 399 or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 738, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 21. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 399 or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 403, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 22. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NOs: 399, 748, 749, 750, 752, the amino acid sequence set forth in or consisting of any one of 754, 756, 758, 759 and 761, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 403, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 23. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NOs: 399, 748, 749, 750, 752, the amino acid sequence set forth in any one of 754, 756, 758, 759 and 761 or consisting of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 738, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 24. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NOs: 399, 748, 749, 750, 752, the amino acid sequence set forth in any one of 754, 756, 758, 759 and 761 or consisting of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 744, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 25. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NOs: 399, 748, 749, 750, 752, the amino acid sequence set forth in any one of 754, 756, 758, 759 and 761 or consisting of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 746, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 26. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 524 or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 528, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 27. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises one of SEQ ID NO.:584, 624, 626 and 628 the amino acid sequence set forth in any one of or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 588, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 28. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NO.: 228, 740, 741, 742 and 743 the amino acid sequence set forth in any one of or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 232, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 29. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NO.: 228, 740, 741, 742 and 743 the amino acid sequence set forth in any one of or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 238, wherein the antibody or antigen-binding fragment is capable of binding to the surface glycoprotein of SARS-CoV-2 expressed on the cell surface of the host cell and/or on the virion.

Embodiment 30. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 32 or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO:36.

Embodiment 31. An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the The light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein the CDRH1, CDRH2 and CDRH3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 33-35, respectively, and the CDRL1, CDRL2 and CDRL3 comprises or consists of the amino acid sequences set forth in SEQ ID NOs: 37-39, respectively.

Embodiment 32. The antibody or antigen-binding fragment of any one of embodiments 3-31, which is capable of neutralizing SARS-CoV-2 infection in an in vitro infection model and/or an in vivo animal infection model and/or in humans.

Embodiment 33. The antibody or antigen-binding fragment of any one of embodiments 1-32, which: (i) Recognize epitopes in the ACE2 receptor binding motif (RBM, SEQ ID NO.: 5) of SARS-CoV-2; (ii) capable of blocking the interaction between SARS-CoV-2 (eg, SARS-CoV-2 RBM) and human ACE2; (iii) capable of binding to the SARS-CoV-2 S protein; (iv) identify epitopes conserved in the ACE2 RBM of SARS-CoV-2 and in the ACE2 RBM of SARS-CoV-1; (v) cross-reacts against SARS-CoV-2 and SARS-CoV-1 coronaviruses; (vii) recognizing an epitope present in the SARS-CoV-2 surface glycoprotein and not present in the ACE2 RBM; (viii) capable of binding to the SARS-CoV-2 S protein trimer in the prefusion conformation; or (ix) any combination of (i)-(viii).

Embodiment 34. The antibody or antigen-binding fragment of any one of embodiments 1-33, which is of the IgG, IgA, IgM, IgE, or IgD isotype.

Embodiment 35. The antibody or antigen-binding fragment of any one of embodiments 1-34, which is an IgG isotype selected from the group consisting of IgGl, IgG2, IgG3, and IgG4.

Embodiment 36. The antibody or antigen-binding fragment of any of embodiments 1-35, which is human, humanized, or chimeric.

Embodiment 37. The antibody or antigen-binding fragment of any one of embodiments 1-36, wherein the antibody or antigen-binding fragment comprises a human antibody, monoclonal antibody, purified antibody, single chain antibody, Fab, Fab', F( ab')2, Fv, scFv or scFab.

Embodiment 38. The antibody or antigen-binding fragment of embodiment 37, wherein the scFv comprises more than one VH domain and more than one VL domain.

Embodiment 39. The antibody or antigen-binding fragment of any one of embodiments 1-38, wherein the antibody or antigen-binding fragment is a multispecific antibody or antigen-binding fragment.

Embodiment 40. The antibody or antigen-binding fragment of embodiment 39, wherein the antibody or antigen-binding fragment is a bispecific antibody or antigen-binding fragment.

Embodiment 41. The antibody or antigen-binding fragment of embodiment 39 or 40, comprising: (i) the first VH and the first VL; and (ii) a second VH and a second VL, wherein the first VH and the second VH are different and each independently comprise at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequence: SEQ ID NO.: 22, 32, 42, 52, 62, 72, 74, 84, 96, 106, 119, 129, 139, 150, 163, 173, 175, 178, 186, 189, 191, 198, 208, 218, 228, 240, 254, 264, 274, 284, 298, 312, 322, 332, 350, 351, 353, 359, 361, 363, 365, 367, 368, 369, 379, 389, 399, 409, 419, 429, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 626, 628, 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 692, 740, 741, 742, 743, 748, 749, 750, 752, 754, 756, 758, 759, 761, 762, and 764, and wherein the first VL and the second VL are different and each independently comprise at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequence: SEQ ID NO.: 26, 36, 46, 56, 66, 78, 88, 94, 100, 110, 123, 133, 143, 154, 157, 168, 194, 196, 202, 212, 222, 232, 238, 244, 250, 252, 258, 268, 278, 288, 294, 296, 302, 308, 310, 316, 326, 336, 355, 357, 373, 383, 393, 403, 413, 423, 438, 448, 458, 468, 478, 488, 498, 508, 518, 528, 538, 548, 558, 568, 578, 588, 598, 608, 618, 686, 696 738, 744 and 746; And wherein the first VH and the first VL together form a first antigen binding site, and wherein the second VH and the second VL together form a second antigen binding site.

Embodiment 42. The antibody or antigen-binding fragment of embodiment 40 or 41, comprising: (i) the first VH and the first VL; and (ii) a second VH and a second VL, wherein the first VH comprises at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences, and the first VL comprises and SEQ The amino acid sequence set forth in any of ID NO.: 143 and 346 has at least 85% (ie, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%) %, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences, and wherein the second VH comprises and SEQ ID NO.: 399, The amino acid sequence set forth in any one of 748, 749, 750, 752, 754, 756, 758, 759, and 761 has at least 85% (e.g., 85%, 86%, 87%, 88%, 89%) %, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences and the second VL comprises have at least 85% (i.e., 85%, 86%, 87%, 88%, 89%, 90%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequences.

Embodiment 43. The antibody or antigen-binding fragment of embodiment 39 or 40, comprising a first antigen-binding portion with a first specificity and a second antigen-binding portion with a second specificity, wherein the first antigen-binding portion Comprising a VH and a VL, the VH comprising or consisting of the amino acid sequence set forth in SEQ ID NO:399, and the VL comprising the amino acid sequence set forth in SEQ ID NO.:738 or SEQ ID NO.:403 sequence or consist of it.

Embodiment 44. The antibody or antigen-binding fragment of embodiment 43, wherein the second antigen-binding portion comprises VH and VL, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 139, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:143.

Embodiment 45. The antibody or antigen-binding fragment of embodiment 43, wherein the second antigen-binding portion comprises VH and VL, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO:342, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO.:346.

Embodiment 46. The antibody or antigen-binding fragment of any one of embodiments 1-45, wherein the antibody or antigen-binding fragment further comprises an Fc polypeptide or fragment thereof.

Embodiment 47. The antibody or antigen-binding fragment of embodiment 46, wherein the Fc polypeptide or fragment thereof comprises: (i) a mutation that enhances binding to FcRn compared to a reference Fc polypeptide that does not contain the mutation; and/or (ii) a mutation that enhances binding to FcyR compared to a reference Fc polypeptide that does not contain the mutation.

Embodiment 48. The antibody or antigen-binding fragment of embodiment 47, wherein the mutation that enhances binding to FcRn comprises: M428L; N434S; N434H; N434A; N434S; M252Y; S254T; T256E; T250Q; P257I; Q311I; D376V; T307A; E380A; or any combination thereof.

Embodiment 49. The antibody or antigen-binding fragment of embodiment 47 or 48, wherein the mutation that enhances binding to FcRn comprises: (i) M428L/N434S; (ii) M252Y/S254T/T256E; (iii) T250Q/M428L (iv) 257I/Q311I; (v) P257I/N434H; (vi) D376V/N434H; (vii) T307A/E380A/N434A; or (viii) any combination of (i)-(vii).

Embodiment 50. The antibody or antigen-binding fragment of any one of embodiments 47-49, wherein the mutation that enhances binding to FcRn comprises M428L/N434S.

Embodiment 51. The antibody or antigen-binding fragment of any one of embodiments 47-50, wherein the mutation that enhances binding to FcyR comprises S239D; I332E; A330L; G236A; or any combination thereof.

Embodiment 52. The antibody or antigen-binding fragment of any one of embodiments 47-51, wherein the mutation that enhances binding to FcγR comprises: (i) S239D/I332E; (ii) S239D/A330L/I332E; (iii) ) G236A/S239D/I332E; or (iv) G236A/A330L/I332E.

Embodiment 53. The antibody or antigen-binding fragment of any one of embodiments 47-52, wherein the Fc polypeptide comprises the L234A mutation and the L235A mutation.

Embodiment 54. The antibody or antigen-binding fragment of any one of embodiments 1-53, comprising a mutation that alters glycosylation, wherein the mutation that alters glycosylation comprises N297A, N297Q or N297G, and/or the antibody Or the antigen-binding fragment is deglycosylated and/or defucosylated.

Embodiment 55. The antibody or antigen-binding fragment of any one of embodiments 1-54, which is capable of binding to SARS-CoV-2 surface glycoprotein with the following EC50: less than 500 ng/ml, less than 250 ng/ml ml, below 100 ng/ml, below 90 ng/ml, below 80 ng/ml, below 70 ng/ml, below 60 ng/ml, below 50 ng/ml, below 40 ng/ml , below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 16 ng/ml, below 15 ng/ml, below 14 ng/ml, below 13 ng/ml, Below 12 ng/ml, Below 10 ng/ml, Below 9 ng/ml, Below 8 ng/ml, Below 7 ng/ml, Below 6 ng/ml, Below 5 ng/ml, Low At 4 ng/ml or less than 2 mg/ml, as measured by ELISA (optionally, indirect ELISA and/or sandwich ELISA) and/or by flow cytometry, wherein the SARS CoV-2 Surface glycoproteins are expressed on the cell surface of host cells.

Embodiment 56. The antibody or antigen-binding fragment of any one of embodiments 1-55, which is capable of binding to the SARS-CoV-2 surface glycoprotein RBD with the following EC50: less than 500 ng/ml, less than 250 ng /ml, below 100 ng/ml, below 90 ng/ml, below 80 ng/ml, below 70 ng/ml, below 60 ng/ml, below 50 ng/ml, below 40 ng/ml ml, less than 30 ng/ml, less than 25 ng/ml, less than 20 ng/ml, less than 16 ng/ml, less than 15 ng/ml, less than 14 ng/ml, less than 13 ng/ml , below 12 ng/ml, below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 ng/ml, Below 4 ng/ml or below 2 mg/ml, as measured by ELISA (optionally, indirect ELISA and/or sandwich ELISA) and/or by flow cytometry, wherein the SARS CoV- 2 Surface glycoproteins are expressed on the cell surface of host cells.

Embodiment 57. The antibody or antigen-binding fragment of any one of embodiments 1-56, which is capable of binding to SARS-CoV-2 RBD with a KD of: below 5×10 ⁻⁸ M, below 4×10 ^-8 M, below 3×10 ^-8 M, below 2×10 ^-8 M, below 1×10 ^-8 M, below 5×10 ^-9 M, below 1×10 ^-9 M, low Below 5×10 ^-10 M, below 1×10 ^-10 M, below 5×10 ^-11 M, below 1×10 ^-11 M, below 5×10 ^-12 M or below 1×10 ^{- 12} M, as determined using Biolayer Interferometry (BLI), optionally using an Octet instrument in which the antibody or antigen-binding fragment is optionally loaded on a protein A needle at 2.7 µg/ml, and SARS- CoV-2 RBD was loaded at 6 µg/ml, 1.5 µg/ml or 0.4 µg/ml for 5 minutes, and further dissociation was optionally measured for 7 minutes.

Embodiment 58. The antibody or antigen-binding fragment of any one of embodiments 1-57, which is capable of binding to SARS-CoV-2 RBD with the following KD: below 6×10 ⁻⁸ M, below 5×10 ^-8 M, below 4×10 ^-8 M, below 3×10 ^-8 M, below 2×10 ^-8 M, below 1×10 ^-8 M, below 5×10 ^-9 M, low below 4×10 ^-9 M, below 3×10 ^-9 M, below 2×10 ^-9 M, below 1×10 ^-9 M or below 8×10 ^-10 M, eg using surface plasmons Resonance (SPR), optionally determined using a single cycle kinetic method using a Biacore T200 instrument.

Embodiment 59. The antibody or antigen-binding fragment of any one of technical solutions 1-58, which can bind to SARS-CoV-2 RBD, and inhibit (i) this RBD and (ii) human ACE2 and/or human SIGLEC -1 interactions.

Embodiment 60. The antibody or antigen-binding fragment of any one of embodiments 1-59, which is capable of neutralizing: (i) Infection by SARS-CoV-2 pseudovirus, optionally: (i)(a) wherein the neutralization IC50 is less than 100 ng/ml, less than 90 ng/ml, less than 80 ng/ml, less than 70 ng/ml, less than 60 ng/ml, less than 50 ng /ml, below 40 ng/ml, below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 15 ng/ml, below 10 ng/ml, below 9 ng/ml ml, less than 8 ng/ml, less than 7 ng/ml, less than 6 ng/ml, less than 5 ng/ml, less than 4 ng/ml, less than 3 ng/ml, less than 2 ng/ml or below 1 ng/ml, preferably below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 ng/ml ml, less than 4 ng/ml, less than 3 ng/ml, less than 2 ng/ml, or less than 1 ng/ml, and/or (i)(b) wherein the neutralization IC80 is less than 100 ng/ml, less than 90 ng/ml, less than 80 ng/ml, less than 70 ng/ml, less than 60 ng/ml, less than 50 ng /ml, less than 40 ng/ml, less than 30 ng/ml or less than 25 ng/ml, preferably less than 50 ng/ml, less than 40 ng/ml, less than 30 ng/ml or less than 25 ng/ml ng/ml, and/or (i)(c) wherein the neutralization EC90 is less than 300 ng/ml, less than 200 ng/ml, less than 100 ng/ml, less than 90 ng/ml, less than 80 ng/ml, less than 70 ng /ml, less than 60 ng/ml 50 ng/ml, less than 40 ng/ml, less than 30 ng/ml, less than 25 ng/ml, less than 20 ng/ml, less than 15 ng/ml or low at 10 ng/ml, wherein further optionally, the SARS-CoV-2 pseudovirus comprises VSV pseudovirus and/or MLV pseudovirus, and/or (i)(d) the SARS-CoV-2 pseudovirus comprises VSV pseudovirus and/or MLV pseudovirus; and/or (ii) infection by live SARS-CoV-2, optionally (ii)(a) wherein the EC50 is less than 60 ng/ml, less than 50 ng/ml, less than 40 ng/ml, less than 30 ng/ml, less than 25 ng/ml, less than 20 ng/ml , below 15 ng/ml, below 12 ng/ml, below 11 ng/ml, below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, Below 6 ng/ml, below 5/ng ml or below 4 ng/ml, preferably below 15 ng/ml, below 12 ng/ml, below 11 ng/ml, below 10 ng/ml , less than 9 ng/ml, less than 8 ng/ml, less than 7 ng/ml, less than 6 ng/ml, less than 5/ng ml, or less than 4 ng/ml, and/or (ii)(b) wherein the EC90 is less than 50 ng/ml, less than 40 ng/ml, less than 35 ng/ml, less than 30 ng/ml, less than 25 ng/ml, less than 20 ng/ml , below 15 ng/ml, below 12 ng/ml, below 11 ng/ml, below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, Below 6 ng/ml, below 5/ng ml or below 4 ng/ml, preferably below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 15 ng/ml or less than 12 ng/ml, and/or (ii) (c) over a period of 6 hours, wherein the infection multiplier is 0.1; and/or (iii) by expression, infection of live SARS-CoV-2 in host cells (eg, HEK293T cells) optionally engineered to overexpress DC-SIGN, L-SIGN, SIGLEC or ACE2; and/or (iv) infection by live SARS-CoV-2 in host cells (eg, HEK293T cells), optionally engineered to overexpress SIGLEC-1 or ACE2, by expression, wherein neutralizing infection comprises fully neutralizing infection .

Embodiment 61. The antibody or antigen-binding fragment of any one of embodiments 1-60, which is capable of neutralizing a SARS-CoV-2 surface glycoprotein comprising one of SEQ ID NO.:3 on the surface glycoprotein. Infection by SARS-CoV-2 variants containing any of the following mutations: N501Y; S477N; N439K; L452R; E484K; K417N; T478K; S494P; A520S; N501T; A522S; Y453F; P384L.

Embodiment 62. The antibody or antigen-binding fragment of embodiment 61, which is capable of neutralizing infection caused by the SARS-CoV-2 variant with an efficacy greater than that of the antibody or antigen-binding fragment by comprising SARS-CoV-2 of the surface glycoprotein amino acid sequence set forth in SEQ ID NO.:3 is less than 3-fold less potent for infection by SARS-CoV-2.

Embodiment 63. The antibody or antigen-binding fragment of any one of embodiments 1-62, which is capable of activating FcyRIIa, FcyRIIIa, or both, wherein optionally: (i) the FcyRIIa comprises an H131 counterpart gene; and/or (ii) the FcγRIIIa comprises the V158 counterpart gene; and/or (iii) Activation was determined using target cells expressing SARS-CoV-2 S, such as CHO cells, and reporter cells expressing NFAT-driven reporters, such as luciferase.

Embodiment 64. The antibody or antigen-binding fragment of any one of embodiments 1-63, comprising: (a) the CH1-CH3 amino acid sequence set forth in SEQ ID NO.:6 and the CL amino acid sequence set forth in SEQ ID NO.:8; (b) the CH1-CH3 amino acid sequence set forth in SEQ ID NO.:6 and the CL amino acid sequence set forth in SEQ ID NO.:9; (c) the CH1-CH3 amino acid sequence set forth in SEQ ID NO.:7 and the CL amino acid sequence set forth in SEQ ID NO.:8; or (d) The CH1-CH3 amino acid sequence set forth in SEQ ID NO.:7 and the CL amino acid sequence set forth in SEQ ID NO.:9.

Embodiment 65. An isolated antibody comprising: (i) the heavy chain amino acid sequence set forth in SEQ ID NO.:767; and (ii) the light chain amino acid sequence set forth in SEQ ID NO.:768.

Embodiment 66. The antibody or antigen-binding fragment of any one of embodiments 1-65, which has an in vivo half-life in a non-human primate of between 20 and 30 days, or between 22 and 28 days , or between 23 and 27 days, or between 24 and 26 days, or about 25 days.

Embodiment 67. The antibody or antigen-binding fragment of any one of embodiments 1-66, wherein the antibody or antigen-binding fragment is capable of neutralizing SARS-CoV-2 infection and/or with an IC50 of about 20 to about 30 ng/ml Or neutralize infection of target cells.

Embodiment 68. The antibody or antigen-binding fragment of any one of embodiments 1-66, wherein the antibody or antigen-binding fragment is capable of neutralizing SARS-CoV-2 infection and/or with an IC50 of about 10 to about 20 ng/ml Or neutralize infection of target cells.

Embodiment 69. The antibody or antigen-binding fragment of any one of embodiments 1-66, wherein the antibody or antigen-binding fragment is capable of neutralizing SARS-CoV-2 infection and/or with an IC50 of about 5 to about 10 ng/ml Or neutralize infection of target cells.

Embodiment 70. The antibody or antigen-binding fragment of any one of embodiments 1-66, wherein the antibody or antigen-binding fragment is capable of neutralizing SARS-CoV-2 infection and/or with an IC50 of about 1 to about 5 ng/ml Or neutralize infection of target cells.

Embodiment 71. The antibody or antigen-binding fragment of any one of embodiments 1-70, wherein the antibody or antigen-binding fragment is capable of neutralizing infection caused by SARS-CoV-2 and does not compete with human ACE2 for binding to The SARS-CoV-2 S protein, Wherein optionally, the neutralization comprises neutralizing infection in an in vitro infection model.

Embodiment 72. An antibody or antigen-binding fragment thereof that competes with the antibody or antigen-binding fragment of any one of embodiments 1-71 for binding to a SARS-CoV-2 surface glycoprotein.

Embodiment 73. An isolated polynucleotide encoding the antibody or antigen-binding fragment of any one of embodiments 1-72, or encoding the VH, heavy chain, VL and/or of the antibody or antigen-binding fragment light chain.

Embodiment 74. The polynucleotide of embodiment 73, wherein the polynucleotide comprises deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), wherein the RNA optionally comprises messenger ribonucleic acid (mRNA).

Embodiment 75. The polynucleotide of embodiment 73 or 74, which is codon-optimized for expression in a host cell.

Embodiment 76. The polynucleotide of any one of embodiments 73 to 75, comprising at least 50%, at least 55%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% consistent, or including according to any of the following A polynucleotide of or consisting of one or more of the polynucleotide sequences: SEQ ID NO.: 30, 31, 40, 41, 50, 51, 60, 61, 70, 71, 73, 82 , 83, 92, 93, 95, 104, 105, 114, 115, 116, 117, 118, 127, 128, 137, 138, 206, 207, 216, 217, 226, 227, 236, 237, 239, 248 , 249, 251, 253, 262, 263, 272, 273, 282, 283, 292, 293, 295, 297, 306, 307, 309, 311, 320, 321, 330, 331, 340, 341, 377, 378 , 387, 388, 397, 398, 407, 408, 417, 418, 427, 428, 433, 442, 443, 452, 453, 462, 463, 472, 473, 482, 483, 492, 493, 502, 503 , 512, 513, 552, 523, 532, 533, 542, 543, 552, 553, 562, 563, 572, 573, 582, 583, 592, 593, 602, 603, 612, 613, 622, 623, 690 , 691, 700-737 and 739.

Embodiment 77. The polynucleotide of any one of embodiments 73-76, comprising: (i) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85% of the nucleotide sequence set forth in SEQ ID NO.:407 %, at least 90%, at least 95%, at least 97%, or at least 99% identical, or a polynucleotide comprising or consisting of the nucleotide sequence set forth in SEQ ID NO.:407; and (ii) having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80% of the nucleotide sequence set forth in SEQ ID NO.: 408, 737 or 739 %, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identical, or a polycore comprising the nucleotide sequence set forth in SEQ ID NO.:408, 737 or 739 Glycosides or consist of them.

Embodiment 78. A recombinant vector comprising the polynucleotide of any one of embodiments 73-77.

Embodiment 79. A host cell comprising the polynucleotide of any one of embodiment 77 and/or the vector of embodiment 78, wherein the polynucleotide is heterologous to the host cell.

Embodiment 80. A human B cell comprising the polynucleotide of any one of embodiments 73-77, wherein the polynucleotide is heterologous to the human B cell and/or wherein the human B cell for immortality.

Embodiment 81. A composition comprising: (i) the antibody or antigen-binding fragment of any one of embodiments 1-72; (ii) the polynucleotide of any one of embodiments 73-77; (iii) the recombinant vector of Example 78; (iv) the host cell of Example 79; and/or (v) the human B cell of Example 80, and a pharmaceutically acceptable excipient or carrier or thinner.

Embodiment 82. The composition of embodiment 81, comprising two or more antibodies or antigen-binding fragments of any one of embodiments 1-72.

Embodiment 83. The composition of embodiment 82, comprising: (i) a first antibody or antigen-binding fragment comprising VH and VL, the VH comprising or consisting of the amino acid sequence as set forth in SEQ ID NO:32, and the VL comprising or consisting of as SEQ ID NO:36 The amino acid sequence composition set forth in; and (ii) a second antibody or antigen-binding fragment comprising VH and VL, the VH comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 139, and the VL comprising or consisting of as SEQ ID NO: 143 The amino acid sequence composition described in .

Embodiment 84. The composition of embodiment 82, comprising: (i) a first antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the light The chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein the CDRH1, CDRH2 and CDRH3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 33-35, respectively, and the CDRL1, CDRL2 and CDRL3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 37-39, respectively; and (ii) a second antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the light The chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein the CDRH1, CDRH2 and CDRH3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 140-142, respectively, and the CDRL1, CDRL2 and CDRL3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 144-146, respectively.

Embodiment 85. The composition of embodiment 82, comprising: (i) a first antibody or antigen-binding fragment comprising a VH and a VL, the VH comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 139 or 342, and the VL comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 139 or 342 : the amino acid sequence composition set forth in 143 or 346; and (ii) a second antibody or antigen-binding fragment comprising a VH and a VL comprising or consisting of as set forth in SEQ ID NO: 399, 748, 749, 750, 752, 754, 756, 758, 759 or 761 consists of an amino acid sequence, and the VL comprises or consists of an amino acid sequence as set forth in SEQ ID NO: 403, 744 or 746.

Embodiment 86. The composition of embodiment 82, comprising: (i) a first antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the light The chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein the CDRH1, CDRH2 and CDRH3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 140-142 or 343-345, respectively, and the CDRL1, CDRL2 and CDRL3 comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 144-146, respectively; and (ii) a second antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising CDRH1, CDRH2 and CDRH3, and the light The chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein the CDRH1, CDRH2 and CDRH3 comprise the amine set forth in any of SEQ ID NOs: 400, 401 and 751, 753, 755, 757, 760, respectively amino acid sequence, and the CDRL1, CDRL2 and CDRL3 comprise or consist of the amino acid sequence set forth in any one of SEQ ID NOs: 404, 405 and 406, 745 and 747, respectively.

Embodiment 87. A composition comprising: (i) a primary antibody or antigen-binding fragment comprising (i) (a) a VH comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 32, and (i) (b) a VL comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 36; and (ii) a second antibody or antigen-binding fragment comprising (ii) (a) a VH comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 139, and (ii) (b) a VL comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 143.

Embodiment 88. A composition comprising: (i) a primary antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein, and comprising (i) (a) a VH comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences set forth in SEQ ID NO.: 400, 402 and 766, respectively, and (i) (b) VL comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NO.: 404, 405 and 406, respectively; and (ii) a second antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein, and comprising (ii) (a) a VH comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences set forth in SEQ ID NO.: 140, 141 or 344 and 142, respectively, and (ii) (b) VL comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NO.: 144, 145 and 146, respectively.

Embodiment 89. A composition comprising: (i) a primary antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein, and comprising (i) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO.:399, and (i) (b) a VL comprising the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738; and (ii) a second antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein, and comprising (ii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO.: 139 or 342, and (ii) (b) a VL comprising the amino acid sequence set forth in SEQ ID NO.:143.

Embodiment 90. The composition of any one of embodiments 82-89, wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment each comprise an IgGl Fc polypeptide comprising the M428L mutation and the N434S mutation.

Embodiment 91. The composition of any one of embodiments 82 to 90, wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment each comprise an IgG1 Fc polypeptide comprising the G236A mutation, the A330L mutation, and I332E mutation.

Embodiment 92. A composition comprising the polynucleotide of any one of embodiments 73 to 77 encapsulated in a carrier molecule, wherein the carrier molecule optionally comprises a lipid, a lipid-derived delivery vehicle Agents such as liposomes, solid lipid nanoparticles, oily suspensions, submicron lipid emulsions, lipid microbubbles, inverse lipid micelles, cochlear liposomes, lipid microtubules, lipid micropillars, lipid nanoparticles (LNPs) or nanoscale platforms.

Embodiment 93. A composition comprising: (i) a primary antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with a protein selected from the group consisting of ACE2, DC-SIGN, L-SIGN and SIGLEC- 1. The interaction between the first cell surface receptor; and (ii) a secondary antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with the group consisting of ACE2, DC-SIGN, L-SIGN and SIGLEC- 1. Interactions between second cell surface receptors, wherein the first cell surface receptor is different from the second cell surface receptor.

Embodiment 94. A method of treating a coronavirus infection, such as a SARS-CoV-2 infection in an individual, the method comprising administering to the individual an effective amount of: (i) the antibody of any one of embodiments 1 to 72 or antigen-binding fragment; (ii) the polynucleotide of any one of Examples 73 to 77; (iii) the recombinant vector of Example 78; (iv) the host cell of Example 79; (v) as implemented The human B cell of Example 80; and/or (vi) the composition of any one of Examples 81-93.

Embodiment 95. A method of treating a coronavirus infection, such as a SARS-CoV-2 infection in an individual, the method comprising administering to the individual: (i) a primary antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein, and comprising (i) (a) a VH comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences set forth in SEQ ID NO.: 400, 402 and 766, respectively, and (i) (b) VL comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NO.: 404, 405 and 406, respectively; and (ii) a second antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein, and comprising (ii) (a) a VH comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences set forth in SEQ ID NO.: 140, 141 or 344 and 142, respectively, and (ii) (b) VL comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NO.: 144, 145 and 146, respectively.

Embodiment 96. A method of treating a coronavirus infection, such as a SARS-CoV-2 infection in an individual, the method comprising administering to the individual: (i) a primary antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein, and comprising (i) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO.:399, and (i) (b) a VL comprising the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738; and (ii) a second antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein, and comprising (ii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO.: 139 or 342, and (ii) (b) a VL comprising the amino acid sequence set forth in SEQ ID NO.:143.

Embodiment 97. A method of preventing or treating or neutralizing a coronavirus infection in an individual, the method comprising administering to an individual who has received a first antibody or antigen-binding fragment a second antibody or antigen-binding fragment, the first antibody or antigen The binding fragment contains: (i) (a) VH and VL amino acid sequences according to SEQ ID NO.: 32 and 36, respectively; or (i) (b) CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NO.: 33-35 and 37-39, respectively; The second antibody or antigen-binding fragment comprises: (ii) (a) the VH amino acid sequence according to SEQ ID NO.: 139 and the VL amino acid sequence according to SEQ ID NO: 143; or (ii)(b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to SEQ ID NOs: 140-142, respectively, and CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NOs: 144-146, respectively.

Embodiment 98. A method of preventing or treating or neutralizing a coronavirus infection in an individual, the method comprising administering to an individual who has received a first antibody or antigen-binding fragment a second antibody or antigen-binding fragment, the first antibody or antigen The binding fragment contains: (i) (a) the VH amino acid sequence according to SEQ ID NO.: 139 and the VL amino acid sequence according to SEQ ID NO: 143; or (i) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to SEQ ID NOs: 140-142, respectively; and CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NOs: 144-146, respectively; The second antibody or antigen-binding fragment comprises: (ii) (a) the VH and VL amino acid sequences according to SEQ ID NO.: 32 and 36, respectively; or (ii) (b) CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NO.: 33-35 and 37-39, respectively.

Embodiment 99. A method of preventing or treating or neutralizing a coronavirus infection in an individual, the method comprising administering to an individual who has received a first antibody or antigen-binding fragment a second antibody or antigen-binding fragment, the first antibody or antigen The binding fragment contains: (i) (a) the VH amino acid sequence according to SEQ ID NO.: 139 or 342 and the VL amino acid sequence according to SEQ ID NO: 143 or 346; or (i) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to SEQ ID NOs: 140-142 or 343-345, respectively; and CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NOs: 144-146, respectively sequence; The second antibody or antigen-binding fragment comprises: (ii) (a) VH amino acid sequence according to SEQ ID NO: 399, 748, 749, 750, 752, 754, 756, 758, 759 or 761, and VL according to SEQ ID NO: 403, 744 or 746 amino acid sequence; or (ii) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to any one of SEQ ID NOs: 400, 401 and 751, 753, 755, 757, 760, respectively, and according to SEQ ID NO: 404, CDRL1, CDRL2 and CDRL3 amino acid sequences of any of 405 and 406, 745 and 747.

Embodiment 100. A method of preventing or treating or neutralizing a coronavirus infection in an individual, the method comprising administering to an individual who has received a first antibody or antigen-binding fragment a second antibody or antigen-binding fragment, the first antibody or antigen-binding fragment The binding fragment contains: (i) (a) VH amino acid sequence according to SEQ ID NO: 399, 748, 749, 750, 752, 754, 756, 758, 759 or 761, and VL according to SEQ ID NO: 403, 744 or 746 amino acid sequence; or (i) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to any one of SEQ ID NOs: 400, 401 and 751, 753, 755, 757, 760, respectively, and according to SEQ ID NO: 404, CDRL1, CDRL2 and CDRL3 amino acid sequences of any of 405 and 406, 745 and 747; The second antibody or antigen-binding fragment comprises: (ii) (a) the VH amino acid sequence according to SEQ ID NO.: 139 or 342 and the VL amino acid sequence according to SEQ ID NO: 143 or 346; or (ii) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to SEQ ID NOs: 140-142 or 343-345, respectively; and CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NOs: 144-146, respectively sequence.

Embodiment 101. The method of any one of embodiments 95-100, wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment each comprise an IgGl Fc polypeptide comprising the M428L mutation and the N434S mutation.

Embodiment 102. The method of any one of embodiments 95-101, wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment each comprise an IgGl Fc polypeptide comprising the G236A mutation, the A330L mutation, and the I332E mutation.

Embodiment 103. A method of treating SARS-CoV-2 infection in an individual, the method comprising administering to the individual: (i) a primary antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with a protein selected from the group consisting of ACE2, DC-SIGN, L-SIGN and SIGLEC- 1. The interaction between the first cell surface receptor; and (ii) a secondary antibody or antigen-binding fragment capable of binding to the SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with the group consisting of ACE2, DC-SIGN, L-SIGN and SIGLEC- 1. Interactions between second cell surface receptors, wherein the first cell surface receptor is different from the second cell surface receptor.

Embodiment 104. The antibody or antigen-binding fragment of any one of technical solutions 1-72, the polynucleotide of any one of embodiments 73 to 77, the recombinant vector of embodiment 78, the host of embodiment 79 A cell, a human B cell as in Example 80, and/or a composition as in any one of Examples 81 to 93, for use in a method of treating a SARS-CoV-2 infection in an individual.

Embodiment 105. The antibody or antigen-binding fragment of any one of technical solutions 1-72, the polynucleotide of any one of embodiments 73 to 77, the recombinant vector of embodiment 78, the embodiment of embodiment 79 A host cell, a human B cell as in Example 80, and/or a composition as in any one of Examples 81 to 93, for use in the preparation of a human B cell for the treatment of a coronavirus (eg, SARS-CoV-2) infection in an individual Pharmacy.

Embodiment 106. A method for in vitro diagnosis of coronavirus (eg, SARS-CoV-2) infection, the method comprising: (i) contacting a sample from an individual with the antibody or antigen-binding fragment of any one of embodiments 1-72; and (ii) detecting a complex comprising the antigen and the antibody, or comprising the antigen and the antigen-binding fragment.

Embodiment 107. The method of embodiment 106, wherein the sample comprises blood isolated from the individual.surface 2 . sequence sequence description SEQ ID NO. sequence Genome sequence of SARS-CoV-2 pneumonia virus isolate Wuhan-Hu-1 in Wuhan seafood market (GenBank: MN908947.3; January 23, 2020) 1 1 attaaaggtt tataccttcc caggtaacaa accaaccaac tttcgatctc ttgtagatct 61 gttctctaaa cgaactttaa aatctgtgtg gctgtcactc ggctgcatgc ttagtgcact 121 cacgcagtat aattaataac taattactgt cgttgacagg acacgagtaa ctcgtctatc 181 ttctgcaggc tgcttacggt ttcgtccgtg ttgcagccga tcatcagcac atctaggttt 241 cgtccgggtg tgaccgaaag gtaagatgga gagccttgtc cctggtttca acgagaaaac 301 acacgtccaa ctcagtttgc ctgttttaca ggttcgcgac gtgctcgtac gtggctttgg 361 agactccgtg gaggaggtct tatcagaggc cgtcaacat cttaaagatg gcacttgtgg 421 cttagtagaa gttgaaaaag gcgttttgcc tcaacttgaa cagccctatg tgttcatcaa 481 acgttcggat gctcgaactg cacctcatgg tcatgttatg gttgagctgg tagcagaact 541 cgaaggcatt cagtacggtc gtagtggtga gacacttggt gtccttgtcc ctcatgtggg 601 cgaaatacca gtggcttacc gcaaggttct tcttcgtaag aacggtaata aaggagctgg 661 tggccatagt tacggcgccg atctaaagtc atttgactta ggcgacgagc ttggcactga 721 tccttatgaa gattttcaag aaaactggaa cactaaacat agcagtggtg ttacccgtga 781 actcatgcgt gagcttaacg gaggggcata cactcgctat gtcgataaca acttctgtgg 841 ccctgatggc taccctctt g agtgcattaa agaccttcta gcacgtgctg gtaaagcttc 901 atgcactttg tccgaacaac tggactttat tgacactaag aggggtgtat actgctgccg 961 tgaacatgag catgaaattg cttggtacac ggaacgttct gaaaagagct atgaattgca 1021 gacacctttt gaaattaaat tggcaaagaa atttgacacc ttcaatgggg aatgtccaaa 1081 ttttgtattt cccttaaatt ccataatcaa gactattcaa ccaagggttg aaaagaaaaa 1141 gcttgatggc tttatgggta gaattcgatc tgtctatcca gttgcgtcac caaatgaatg 1201 caaccaaatg tgcctttcaa ctctcatgaa gtgtgatcat tgtggtgaaa cttcatggca 1261 gacgggcgat tttgttaaag ccacttgcga attttgtggc actgagaatt tgactaaaga 1321 aggtgccact acttgtggtt acttacccca aaatgctgtt gttaaaattt attgtccagc 1381 atgtcacaat tcagaagtag gacctgagca tagtcttgcc gaataccata atgaatctgg 1441 cttgaaaacc attcttcgta agggtggtcg cactattgcc tttggaggct gtgtgttctc 1501 ttatgttggt tgccataaca agtgtgccta ttgggttcca cgtgctagcg ctaacatagg 1561 ttgtaaccat acaggtgttg ttggagaagg ttccgaaggt cttaatgaca accttcttga 1621 aatactccaa aaagagaaag tcaacatcaa tattgttggt gactttaaac ttaatgaaga 1681 gatcgccatt attttggcat cttttt ctgc ttccacaagt gcttttgtgg aaactgtgaa 1741 aggtttggat tataaagcat tgttgaatcc tgtggtaatt ttaaagttac 1801 aaaaggaaaa gctaaaaaag gtgcctggaa tattggtgaa cagaaatcaa tactgagtcc 1861 tctttatgca tttgcatcag aggctgctcg tgttgtacga tcaattttct cccgcactct 1921 tgaaactgct caaaattctg tgcgtgtttt acagaaggcc gctataacaa tactagatgg 1981 aatttcacag tattcactga gactcattga tgctatgatg ttcacatctg atttggctac 2041 taacaatcta gttgtaatgg cctacattac aggtggtgtt gttcagttga cttcgcagtg 2101 gctaactaac atctttggca ctgtttatga tcaaacaaat aaaactcaaa cccgtccttg attggcttga 2161 agagaagttt aaggaaggtg tagagtttct tagagacggt tgggaaattg ttaaatttat 2221 ctcaacctgt gcttgtgaaa ttgtcggtgg acaaattgtc acctgtgcaa aggaaattaa 2281 ggagagtgtt cagacattct ttaagcttgt aaataaattt ttggctttgt gtgctgactc 2341 tatcattatt ggtggagcta aacttaaagc cttgaattta ggtgaaacat ttgtcacgca 2401 ctcaaaggga ttgtacagaa agtgtgttaa atccagagaa gaaactggcc tactcatgcc 2461 tctaaaagcc ccaaaagaaa ttatcttctt agagggagaa acacttccca cagaagtgtt 2521 aacagaggaa gttgtcttga aaactggtga t ttacaacca ttagaacaac ctactagtga 2581 agctgttgaa gctccattgg ttggtacacc agtttgtatt aacgggctta tgttgctcga 2641 aatcaaagac acagaaaagt actgtgccct tgcacctaat atgatggtaa caaacaatac 2701 cttcacactc aaaggcggtg caccaacaaa ggttactttt ggtgatgaca ctgtgataga 2761 agtgcaaggt tacaagagtg tgaatatcac ttttgaactt gatgaaagga ttgataaagt 2821 acttaatgag aagtgctctg cctatacagt tgaactcggt acagaagtaa atgagttcgc 2881 ctgtgttgtg gcagatgctg tcataaaaac tttgcaacca gtatctgaat tacttacacc 2941 actgggcatt gatttagatg agtggagtat ggctacatac tacttatttg atgagtctgg 3001 tgagtttaaa ttggcttcac atatgtattg ttctttctac cctccagatg aggatgaaga 3061 agaaggtgat tgtgaagaag aagagtttga gccatcaact caatatgagt atggtactga 3121 agatgattac caaggtaaac ctttggaatt tggtgccact tctgctgctc ttcaacctga 3181 agaagagcaa gaagaagatt ggttagatga tgatagtcaa caaactgttg gtcaacaaga 3241 cggcagtgag gacaatcaga caactactat tcaaacaatt gttgaggttc aacctcaatt 3301 agagatggaa cttacaccag ttgttcagac tattgaagtg aatagtttta gtggttattt 3361 aaaacttact gacaatgtat acattaaaaa tgcagac att gtggaagaag ctaaaaaggt 3421 aaaaccaaca gtggttgtta atgcagccaa tgtttacctt aaacatggag gaggtgttgc 3481 aggagcctta aataaggcta ctaacaatgc catgcaagtt gaatctgatg attacatagc 3541 tactaatgga ccacttaaag tgggtggtag ttgtgtttta agcggacaca atcttgctaa 3601 acactgtctt catgttgtcg gcccaaatgt taacaaaggt gaagacattc aacttcttaa 3661 gagtgcttat gaaaatttta atcagcacga agttctactt gcaccattat tatcagctgg 3721 tatttttggt gctgacccta tacattcttt aagagtttgt gtagatactg ttcgcacaaa 3781 tgtctactta gctgtctttg ataaaaatct ctatgacaaa cttgtttcaa gctttttgga 3841 aatgaagagt gaaaagcaag ttgaacaaaa gatcgctgag attcctaaag aggaagttaa 3901 gccatttata actgaaagta aaccttcagt tgaacagaga aaacaagatg ataagaaaat 3961 caaagcttgt gttgaagaag ttacaacaac tctggaagaa actaagttcc tcacagaaaa 4021 cttgttactt tatattgaca ttaatggcaa tcttcatcca gattctgcca ctcttgttag 4081 tgacattgac atcactttct taaagaaaga tgctccatat atagtgggtg atgttgttca 4141 agagggtgtt ttaactgctg tggttatacc tactaaaaag gctggtggca ctactgaaat 4201 gctagcgaaa gctttgagaa aagtgccaac agacaattat at aaccactt acccgggtca 4261 gggtttaaat ggttacactg tagaggaggc aaagacagtg cttaaaaagt gtaaaagtgc 4321 cttttacatt ctaccatcta ttatctctaa tgagaagcaa gaaattcttg gaactgtttc 4381 ttggaatttg cgagaaatgc ttgcacatgc agaagaaaca cgcaaattaa tgcctgtctg 4441 tgtggaaact aaagccatag tttcaactat acagcgtaaa tataagggta ttaaaataca 4501 agagggtgtg gttgattatg gtgctagatt ttacttttac accagtaaaa caactgtagc 4561 gtcacttatc aacacactta acgatctaaa tgaaactctt gttacaatgc cacttggcta 4621 tgtaacacat ggcttaaatt tggaagaagc tgctcggtat atgagatctc tcaaagtgcc 4681 agctacagtt tctgtttctt cacctgatgc tgttacagcg tataatggtt atcttacttc 4741 ttcttctaaa acacctgaag aacattttat tgaaaccatc tcacttgctg gttcctataa 4801 agattggtcc tattctggac acagtttggt ccaacttatt tggatggagc aatctacaca actaggtata gaatttctta agagaggtga 4861 taaaagtgta tattacacta gtaatcctac cacattccac ctagatggtg aagttatcac 4921 ctttgacaat cttaagacac ttctttcttt gagagaagtg aggactatta aggtgtttac 4981 aacagtagac aacattaacc tccacacgca agttgtggac atgtcaatga catatggaca 5041 tgatgttact aaaataaa ac ctcataattc 5101 acatgaaggt aaaacatttt atgttttacc taatgatgac actctacgtg ttgaggcttt 5161 tgagtactac cacacaactg atcctagttt tctgggtagg tacatgtcag cattaaatca 5221 cactaaaaag tggaaatacc cacaagttaa tggtttaact tctattaaat gggcagataa 5281 caactgttat cttgccactg cattgttaac actccaacaa atagagttga agtttaatcc 5341 acctgctcta caagatgctt attacagagc aagggctggt gaagctgcta acttttgtgc 5401 acttatctta gcctactgta ataagacagt aggtgagtta ggtgatgtta gagaaacaat 5461 gagttacttg tttcaacatg ccaatttaga ttcttgcaaa agagtcttga acgtggtgtg 5521 taaaacttgt ggacaacagc agacaaccct taagggtgta gaagctgtta tgtacatggg 5581 cacactttct tatgaacaat ttaagaaagg tgttcagata ccttgtacgt gtggtaaaca 5641 agctacaaaa tatctagtac aacaggagtc accttttgtt atgatgtcag caccacctgc 5701 tcagtatgaa 5761 cttaagcatg gtacatttac ttgtgctagt gagtacactg gtaattacca accataaaac cagttactta taaattggat gtgtggtcac tataaacata taacttctaa agaaactttg tattgcatag acggtgcttt 5821 acttacaaag tcctcagaat acaaaggtcc tattacggat gttttctaca aagaaaacag 5881 ttacacaaca ggtgttgttt gta cagaaat 5941 tgaccctaag ttggacaatt attataagaa agacaattct tatttcacag agcaaccaat 6001 tgatcttgta ccaaaccaac catatccaaa cgcaagcttc gataatttta agtttgtatg 6061 tgataatatc aaatttgctg atgatttaaa ccagttaact ggttataaga aacctgcttc 6121 aagagagctt aaagttacat ttttccctga cttaaatggt gatgtggtgg ctattgatta 6181 taaacactac acaccctctt ttaagaaagg agctaaattg ttacataaac ctattgtttg 6241 gcatgttaac aatgcaacta ataaagccac gtataaacca aatacctggt gtatacgttg 6301 tctttggagc acaaaaccag ttgaaacatc aaattcgttt gatgtactga agtcagagga 6361 cgcgcaggga atggataatc ttgcctgcga agatctaaaa ccagtctctg aagaagtagt 6421 ggaaaatcct accatacaga aagacgttct tgagtgtaat gtgaaaacta ccgaagttgt 6481 aggagacatt atacttaaac cagcaaataa tagtttaaaa attacagaag aggttggcca 6541 cacagatcta atggctgctt atgtagacaa ttctagtctt actattaaga aacctaatga 6601 attatctaga gtattaggtt tgaaaaccct tgctactcat ggtttagctg ctgttaatag 6661 tgtcccttgg gatactatag ctaattatgc taagcctttt cttaacaaag ttgttagtac 6721 aactactaac atagttacac ggtgtttaaa ccgtgtttgt actaattata tgccttatt t 6781 ctttacttta ttgctacaat tgtgtacttt tactagaagt acaaattcta gaattaaagc 6841 atctatgccg actactatag caaagaatac tgttaagagt gtcggtaaat tttgtctaga 6901 ggcttcattt aattatttga agtcacctaa tttttctaaa ctgataaata ttataatttg 6961 gtttttacta ttaagtgttt gcctaggttc tttaatctac tcaaccgctg ctttaggtgt 7021 tttaatgtct aatttaggca tgccttctta ctgtactggt tacagagaag gctatttgaa 7081 ctctactaat gtcactattg caacctactg tactggttct ataccttgta gtgtttgtct 7141 tagtggttta gattctttag acacctatcc ttctttagaa actatacaaa ttaccatttc 7201 atcttttaaa tgggatttaa ctgcttttgg cttagttgca gagtggtttt tggcatatat 7261 tcttttcact aggtttttct atgtacttgg attggctgca atcatgcaat tgtttttcag 7321 ctattttgca gtacatttta ttagtaattc ttggcttatg tggttaataa ttaatcttgt 7381 acaaatggcc ccgatttcag ctatggttag aatgtacatc ttctttgcat cattttatta 7441 tgtatggaaa agttatgtgc atgttgtaga cggttgtaat tcatcaactt gtatgatgtg 7501 ttacaaacgt aatagagcaa caagagtcga atgtacaact attgttaatg gtgttagaag 7561 gtccttttat gtctatgcta atggaggtaa aggcttttgc aaactacaca attggaattg 7621 tgttaattgt gatacattct gtgctggtag tacatttatt agtgatgaag ttgcgagaga 7681 cttgtcacta cagtttaaaa gaccaataaa tcctactgac cagtcttctt acatcgttga 7741 tagtgttaca gtgaagaatg gttccatcca tctttacttt gataaagctg gtcaaaagac 7801 ttatgaaaga cattctctct ctcattttgt taacttagac aacctgagag ctaataacac 7861 taaaggttca ttgcctatta atgttatagt ttttgatggt aaatcaaaat gtgaagaatc 7921 atctgcaaaa tcagcgtctg tttactacag tcagcttatg tgtcaaccta tactgttact 7981 agatcaggca ttagtgtctg atgttggtga tagtgcggaa gttgcagtta aaatgtttga 8041 tgcttacgtt aatacgtttt catcaacttt ttttatttca gcagctcggc aagggtttgt tgattcagat gtagaaacta aagatgttgt 8221 tgaatgtctt aaattgtcac atcaatctga catagaagtt actggcgata gttgtaataa 8281 ctatatgctc acctataaca aagttgaaaa catgacaccc cgtgaccttg gtgcttgtat 8341 tgactgtagt gcgcgtcata ttaatgcgca ggtagcaaaa agtcacaaca ttgctttgat 8401 atggaacgtt aaagatttca tgtcattgtc tgaacaacta cgaaaacaaa tacgtagtgc 8461 tgcta taacgtacca atggaaaaac tcaaaacact 8101 agttgcaact gcagaagctg aacttgcaaa gaatgtgtcc ttagacaatg tcttatctac 8161 aaaag aataacttac cttttaagtt gacatgtgca actactagac aagttgttaa 8521 tgttgtaaca acaaagatag cacttaaggg tggtaaaatt gttaataatt ggttgaagca 8581 gttaattaaa gttacacttg tgttcctttt tgttgctgct attttctatt taataacacc 8641 tgttcatgtc atgtctaaac atactgactt ttcaagtgaa atcataggat acaaggctat 8701 tgatggtggt gtcactcgtg acatagcatc tacagatact tgttttgcta acaaacatgc 8761 tgattttgac acatggttta gccagcgtgg tggtagttat actaatgaca aagcttgccc 8821 attgattgct gcagtcataa caagagaagt gggttttgtc gtgcctggtt tgcctggcac 8881 gatattacgc acaactaatg gtgacttttt gcatttctta cctagagttt ttagtgcagt 8941 tggtaacatc tgttacacac catcaaaact tatagagtac actgactttg caacatcagc 9001 ttgtgttttg gctgctgaat gtacaatttt taaagatgct tctggtaagc cagtaccata 9061 ttgttatgat accaatgtac tagaaggttc tgttgcttat gaaagtttac gccctgacac 9121 acgttatgtg ctcatggatg gctctattat tcaatttcct aacacctacc ttgaaggttc 9181 tgttagagtg gtaacaactt ttgattctga gtactgtagg cacggcactt gtgaaagatc 9241 agaagctggt gtttgtgtat ctactagtgg tagatgggta cttaacaatg attattacag 9301 atctttacca ggagttttct gtggtgtaga tgctgtaaat ttacttacta atatgtttac 9361 accactaatt caacctattg gtgctttgga catatcagca tctatagtag ctggtggtat 9421 tgtagctatc gtagtaacat gccttgccta ctattttatg aggtttagaa gagcttttgg 9481 tgaatacagt catgtagttg cctttaatac tttactattc cttatgtcat tcactgtact 9541 ctgtttaaca ccagtttact cattcttacc tggtgtttat tctgttattt acttgtactt 9601 gacattttat cttactaatg atgtttcttt tttagcacat attcagtgga tggttatgtt 9661 cacaccttta gtacctttct ggataacaat tgcttatatc atttgtattt ccacaaagca 9721 tttctattgg ttctttagta attacctaaa gagacgtgta gtctttaatg gtgtttcctt 9781 tagtactttt gaagaagctg cgctgtgcac ctttttgtta aataaagaaa tgtatctaaa 9841 gttgcgtagt gatgtgctat tacctcttac gcaatataat agatacttag ctctttataa 9901 taagtacaag tattttagtg gagcaatgga tacaactagc tacagagaag ctgcttgttg 9961 tcatctcgca aaggctctca atgacttcag taactcaggt tctgatgttc tttaccaacc 10021 accacaaacc tctatcacct cagctgtttt gcagagtggt tttagaaaaa tggcattccc 10081 atctggtaaa gttgagggtt gtatggtaca agtaacttgt ggtacaacta cacttaacgg 10141 tctttggctt gatgacgtag tttactgtcc aagacatgtg atctgcacct ctgaagacat 10201 gcttaaccct aattatgaag atttactcat tcgtaagtct aatcataatt tcttggtaca 10261 ggctggtaat gttcaactca gggttattgg acattctatg caaaattgtg tacttaagct 10321 taaggttgat acagccaatc ctaagacacc taagtataag tttgttcgca ttcaaccagg 10381 acagactttt tcagtgttag cttgttacaa tggttcacca tctggtgttt accaatgtgc 10441 tatgaggccc aatttcacta ttaagggttc attccttaat ggttcatgtg gtagtgttgg 10501 ttttaacata gattatgact gtgtctcttt ttgttacatg caccatatgg aattaccaac 10561 tggagttcat gctggcacag acttagaagg taacttttat ggaccttttg ttgacaggca 10621 aacagcacaa gcagctggta cggacacaac tattacagtt aatgttttag cttggttgta 10681 cgctgctgtt ataaatggag acaggtggtt tctcaatcga tttaccacaa ctcttaatga 10741 ctttaacctt gtggctatga agtacaatta tgaacctcta acacaagacc atgttgacat 10801 actaggacct ctttctgctc aaactggaat tgccgtttta gatatgtgtg cttcattaaa 10861 agaattactg caaaatggta tgaatggacg taccatattg ggtagtgctt tattagaaga 10921 tgaatttaca ccttttgatg ttgttagaca atgctcaggt gttactttcc aaagtgcagt 10981 gaa aagaaca atcaagggta cacaccactg gttgttactc acaattttga cttcactttt 11041 agttttagtc cagagtactc aatggtcttt gttctttttt ttgtatgaaa atgccttttt 11101 accttttgct atgggtatta ttgctatgtc tgcttttgca atgatgtttg tcaaacataa 11161 gcatgcattt ctctgtttgt ttttgttacc ttctcttgcc actgtagctt attttaatat 11221 ggtctatatg cctgctagtt gggtgatgcg tattatgaca tggttggata tggttgatac 11281 tagtttgtct ggttttaagc taaaagactg tgttatgtat gcatcagctg tagtgttact 11341 aatccttatg acagcaagaa ctgtgtatga tgatggtgct aggagagtgt ggacacttat 11401 gaatgtcttg acactcgttt ataaagttta ttatggtaat gctttagatc aagccatttc 11461 catgtgggct cttataatct ctgttacttc taactactca ggtgtagtta caactgtcat 11521 gtttttggcc agaggtattg tttttatgtg tgttgagtat tgccctattt tcttcataac 11581 tggtaataca cttcagtgta taatgctagt ttattgtttc ttaggctatt tttgtacttg 11641 ttactttggc ctcttttgtt tactcaaccg ctactttaga ctgactcttg gtgtttatga 11701 ttacttagtt tctacacagg agtttagata tatgaattca cagggactac tcccacccaa 11761 gaatagcata gatgccttca aactcaacat taaattgttg ggtgttggtg gcaaaccttg 1 1821 tatcaaagta gccactgtac agtctaaaat gtcagatgta aagtgcacat cagtagtctt 11881 actctcagtt ttgcaacaac tcagagtaga atcatcatct aaattgtggg ctcaatgtgt 11941 ccagttacac aatgacattc tcttagctaa agatactact gaagcctttg aaaaaatggt 12001 ttcactactt tctgttttgc tttccatgca gggtgctgta gacataaaca agctttgtga 12061 agaaatgctg gacaacaggg caaccttaca agctatagcc tcagagttta gttcccttcc 12121 atcatatgca gcttttgcta ctgctcaaga agcttatgag caggctgttg ctaatggtga 12181 ttctgaagtt gttcttaaaa agttgaagaa gtctttgaat gtggctaaat ctgaatttga 12241 ccgtgatgca gccatgcaac gtaagttgga aaagatggct gatcaagcta tgacccaaat 12301 gtataaacag gctagatctg aggacaagag ggcaaaagtt actagtgcta tgcagacaat 12361 gcttttcact atgcttagaa agttggataa tgatgcactc aacaacatta tcaacaatgc 12421 aagagatggt tgtgttccct tgaacataat acctcttaca acagcagcca aactaatggt 12481 tgtcatacca gactataaca catataaaaa tacgtgtgat ggtacaacat ttacttatgc 12541 atcagcattg tgggaaatcc aacaggttgt agatgcagat agtaaaattg ttcaacttag 12601 tgaaattagt atggacaatt cacctaattt agcatggcct cttattgtaa cagc tttaag 12661 ggccaattct gctgtcaaat tacagaataa tgagcttagt cctgttgcac tacgacagat 12721 gtcttgtgct gccggtacta cacaaactgc ttgcactgat gacaatgcgt tagcttacta 12781 caacacaaca aagggaggta ggtttgtact tgcactgtta tccgatttac aggatttgaa 12841 atgggctaga ttccctaaga gtgatggaac tggtactatc tatacagaac tggaaccacc 12901 ttgtaggttt gttacagaca cacctaaagg tcctaaagtg aagtatttat actttattaa 12961 aggattaaac aacctaaata gaggtatggt acttggtagt ttagctgcca cagtacgtct 13021 acaagctggt aatgcaacag aagtgcctgc caattcaact gtattatctt tctgtgcttt 13081 tgctgtagat gctgctaaag cttacaaaga ttatctagct agtgggggac aaccaatcac 13141 taattgtgtt aagatgttgt gtacacacac tggtactggt caggcaataa cagttacacc 13201 ggaagccaat atggatcaag aatcctttgg tggtgcatcg tgttgtctgt actgccgttg 13261 ccacatagat catccaaatc ctaaaggatt ttgtgactta aaaggtaagt atgtacaaat 13321 acctacaact tgtgctaatg accctgtggg ttttacactt aaaaacacag tctgtaccgt 13381 ctgcggtatg tggaaaggtt atggctgtag ttgtgatcaa ctccgcgaac ccatgcttca 13441 gtcagctgat gcacaatcgt ttttaaacgg gtttgcggtg taagtgc agc ccgtcttaca 13501 ccgtgcggca caggcactag tactgatgtc gtatacaggg cttttgacat ctacaatgat 13561 aaagtagctg gttttgctaa attcctaaaa actaattgtt gtcgcttcca agaaaaggac 13621 gaagatgaca atttaattga ttcttacttt gtagttaaga gacacacttt ctctaactac 13681 caacatgaag aaacaattta taatttactt aaggattgtc cagctgttgc taaacatgac 13741 ttctttaagt ttagaataga cggtgacatg gtaccacata tatcacgtca acgtcttact 13801 aaatacacaa tggcagacct cgtctatgct ttaaggcatt ttgatgaagg taattgtgac 13861 acattaaaag aaatacttgt cacatacaat tgttgtgatg atgattattt caataaaaag 13921 gactggtatg attttgtaga aaacccagat atattacgcg tatacgccaa cttaggtgaa 13981 cgtgtacgcc aagctttgtt aaaaacagta caattctgtg atgccatgcg aaatgctggt 14041 attgttggtg tactgacatt agataatcaa gatctcaatg gtaactggta tgatttcggt 14101 gatttcatac aaaccacgcc aggtagtgga gttcctgttg tagattctta ttattcattg 14161 ttaatgccta tattaacctt gaccagggct ttaactgcag agtcacatgt tgacactgac 14221 ttaacaaagc cttacattaa gtgggatttg ttaaaatatg acttcacgga agagaggtta 14281 aaactctttg accgttattt taaatattgg gatcagacat accacccaaa ttgtgttaac 14341 tgtttggatg acagatgcat tctgcattgt gcaaacttta atgttttatt ctctacagtg 14401 ttcccaccta caagttttgg accactagtg agaaaaatat ttgttgatgg tgttccattt 14461 gtagtttcaa ctggatacca cttcagagag ctaggtgttg tacataatca ggatgtaaac 14521 ttacatagct ctagacttag ttttaaggaa ttacttgtgt atgctgctga ccctgctatg 14581 cacgctgctt ctggtaatct attactagat aaacgcacta cgtgcttttc agtagctgca 14641 cttactaaca atgttgcttt tcaaactgtc aaacccggta attttaacaa agacttctat 14701 gactttgctg tgtctaaggg tttctttaag gaaggaagtt ctgttgaatt aaaacacttc 14761 ttctttgctc aggatggtaa tgctgctatc agcgattatg actactatcg ttataatcta 14821 ccaacaatgt gtgatatcag acaactacta tttgtagttg aagttgttga taagtacttt 14881 gattgttacg atggtggctg tattaatgct aaccaagtca tcgtcaacaa cctagacaaa 14941 tcagctggtt ttccatttaa taaatggggt aaggctagac tttattatga ttcaatgagt 15001 tatgaggatc aagatgcact tttcgcatat acaaaacgta atgtcatccc tactataact 15061 caaatgaatc ttaagtatgc cattagtgca aagaatagag ctcgcaccgt agctggtgtc 15121 tctatctgta gtactatgac caatagacag tt tcatcaaa aattattgaa atcaatagcc 15181 gccactagag gagctactgt agtaattgga acaagcaaat tctatggtgg ttggcacaac 15241 atgttaaaaa ctgtttatag tgatgtagaa aaccctcacc ttatgggttg ggattatcct 15301 aaatgtgata gagccatgcc taacatgctt agaattatgg cctcacttgt tcttgctcgc 15361 aaacatacaa cgtgttgtag cttgtcacac cgtttctata gattagctaa tgagtgtgct 15421 caagtattga gtgaaatggt catgtgtggc ggttcactat atgttaaacc aggtggaacc 15481 tcatcaggag atgccacaac tgcttatgct aatagtgttt ttaacatttg tcaagctgtc 15541 acggccaatg ttaatgcact tttatctact gatggtaaca aaattgccga taagtatgtc 15601 cgcaatttac aacacagact ttatgagtgt ctctatagaa atagagatgt tgacacagac 15661 tttgtgaatg agttttacgc atatttgcgt aaacatttct caatgatgat actctctgac 15721 gatgctgttg tgtgtttcaa tagcacttat gcatctcaag gtctagtggc tagcataaag 15781 aactttaagt cagttcttta ttatcaaaac aatgttttta tgtctgaagc aaaatgttgg 15841 actgagactg accttactaa aggacctcat gaattttgct ctcaacatac aatgctagtt 15901 aaacagggtg atgattatgt gtaccttcct tacccagatc catcaagaat cctaggggcc 15961 ggctgttttg tagatgatat cgtaa aaaca gatggtacac ttatgattga acggttcgtg 16021 tctttagcta tagatgctta cccacttact aaacatccta atcaggagta tgctgatgtc 16081 tttcatttgt acttacaata cataagaaag ctacatgatg agttaacagg acacatgtta 16141 gacatgtatt ctgttatgct tactaatgat aacacttcaa ggtattggga acctgagttt 16201 tatgaggcta tgtacacacc gcatacagtc ttacaggctg ttggggcttg tgttctttgc 16261 aattcacaga cttcattaag atgtggtgct tgcatacgta gaccattctt atgttgtaaa 16321 tgctgttacg accatgtcat atcaacatca cataaattag tcttgtctgt taatccgtat 16381 gtttgcaatg ctccaggttg tgatgtcaca gatgtgactc aactttactt aggaggtatg 16441 agctattatt gtaaatcaca taaaccaccc attagttttc cattgtgtgc taatggacaa 16501 gtttttggtt tatataaaaa tacatgtgtt ggtagcgata atgttactga ctttaatgca 16561 attgcaacat gtgactggac aaatgctggt gattacattt tagctaacac ctgtactgaa 16621 agactcaagc tttttgcagc agaaacgctc aaagctactg aggagacatt taaactgtct 16681 tatggtattg ctactgtacg tgaagtgctg tctgacagag aattacatct ttcatgggaa 16741 gttggtaaac ctagaccacc acttaaccga aattatgtct ttactggtta tcgtgtaact 16801 aaaaacagta aagtacaa at aggagagtac acctttgaaa aaggtgacta tggtgatgct 16861 gttgtttacc gaggtacaac aacttacaaa ttaaatgttg gtgattattt tgtgctgaca 16921 tcacatacag taatgccatt aagtgcacct acactagtgc cacaagagca ctatgttaga 16981 attactggct tatacccaac actcaatatc tcagatgagt tttctagcaa tgttgcaaat 17041 tatcaaaagg ttggtatgca aaagtattct acactccagg gaccacctgg tactggtaag 17101 agtcattttg ctattggcct agctctctac tacccttctg ctcgcatagt gtatacagct 17161 tgctctcatg ccgctgttga tgcactatgt gagaaggcat taaaatattt gcctatagat 17221 aaatgtagta gaattatacc tgcacgtgct cgtgtagagt gttttgataa attcaaagtg 17281 aattcaacat tagaacagta tgtcttttgt actgtaaatg cattgcctga gacgacagca 17341 gatatagttg tctttgatga aatttcaatg gccacaaatt atgatttgag tgttgtcaat 17401 gccagattac gtgctaagca ctatgtgtac attggcgacc ctgctcaatt acctgcacca 17461 cgcacattgc taactaaggg cacactagaa ccagaatatt tcaattcagt gtgtagactt 17521 atgaaaacta catgttcctc ggaacttgtc ggcgttgtcc tgctgaaatt aataagctta aagcacataa agacaaatca taggtccaga 17581 gttgacactg tgagtgcttt ggtttatgat 17641 gctcaatgct ttaaaatgtt ttataagggt gttatcacgc atgatgtttc atctgcaatt 17701 aacaggccac aaataggcgt ggtaagagaa ttccttacac gtaaccctgc ttggagaaaa 17761 gctgtcttta tttcacctta taattcacag aatgctgtag cctcaaagat tttgggacta 17821 ccaactcaaa ctgttgattc atcacagggc tcagaatatg actatgtcat attcactcaa 17881 accactgaaa cagctcactc ttgtaatgta aacagattta atgttgctat taccagagca 17941 aaagtaggca tactttgcat aatgtctgat agagaccttt atgacaagtt gcaatttaca 18001 agtcttgaaa ttccacgtag gaatgtggca actttacaag ctgaaaatgt aacaggactc 18061 tttaaagatt gtagtaaggt aatcactggg ttacatccta cacaggcacc tacacacctc 18121 agtgttgaca ctaaattcaa aactgaaggt ttatgtgttg acatacctgg catacctaag 18181 gacatgacct atagaagact catctctatg atgggtttta aaatgaatta tcaagttaat 18241 ggttacccta acatgtttat cacccgcgaa gaagctataa gacatgtacg tgcatggatt 18301 ggcttcgatg tcgaggggtg tcatgctact agagaagctg ttggtaccaa tttaccttta 18361 cagctaggtt tttctacagg tgttaaccta gttgctgtac ctacaggtta tgttgataca 18421 cctaataata cagatttttc cagagttagt gctaaaccac cgcctggaga tcaatttaaa 18481 cac ctcatac cacttatgta caaaggactt ccttggaatg tagtgcgtat aaagattgta 18541 caaatgttaa gtgacacact taaaaatctc tctgacagag tcgtatttgt cttatgggca 18601 catggctttg agttgacatc tatgaagtat tttgtgaaaa taggacctga gcgcacctgt 18661 tgtctatgtg atagacgtgc cacatgcttt tccactgctt cagacactta tgcctgttgg 18721 catcattcta ttggatttga ttacgtctat aatccgttta tgattgatgt tcaacaatgg 18781 ggttttacag gtaacctaca aagcaaccat gatctgtatt gtcaagtcca tggtaatgca 18841 catgtagcta gttgtgatgc aatcatgact aggtgtctag ctgtccacga gtgctttgtt 18901 aagcgtgttg actggactat tgaatatcct ataattggtg atgaactgaa gattaatgcg 18961 gcttgtagaa aggttcaaca catggttgtt aaagctgcat tattagcaga caaattccca 19021 gttcttcacg acattggtaa ccctaaagct attaagtgtg tacctcaagc tgatgtagaa 19081 tggaagttct atgatgcaca gccttgtagt gacaaagctt ataaaataga agaattattc 19141 tattcttatg ccacacattc tgacaaattc acagatggtg tatgcctatt ttggaattgc 19201 aatgtcgata gatatcctgc taattccatt gtttgtagat ttgacactag agtgctatct 19261 aaccttaact tgcctggttg tgatggtggc agtttgtatg taaataaaca tgcattccac 1 9321 acaccagctt ttgataaaag tgcttttgtt aatttaaaac aattaccatt tttctattac 19381 tctgacagtc catgtgagtc tcatggaaaa caagtagtgt cagatataga ttatgtacca 19441 ctaaagtctg ctacgtgtat aacacgttgc aatttaggtg gtgctgtctg tagacatcat 19501 gctaatgagt acagattgta tctcgatgct tataacatga tgatctcagc tggctttagc 19561 ttgtgggttt acaaacaatt tgatacttat aacctctgga acacttttac aagacttcag 19621 agtttagaaa atgtggcttt taatgttgta aataagggac actttgatgg acaacagggt 19681 gaagtaccag tttctatcat taataacact gtttacacaa aagttgatgg tgttgatgta 19741 gaattgtttg aaaataaaac aacattacct gttaatgtag catttgagct ttgggctaag 19801 cgcaacatta aaccagtacc agaggtgaaa atactcaata atttgggtgt ggacattgct 19861 gctaatactg tgatctggga ctacaaaaga gatgctccag cacatatatc tactattggt 19921 gtttgttcta tgactgacat agccaagaaa ccaactgaaa cgatttgtgc accactcact 19981 gtcttttttg atggtagagt tgatggtcaa gtagacttat ttagaaatgc ccgtaatggt 20041 gttcttatta cagaaggtag tgttaaaggt ttacaaccat ctgtaggtcc caaacaagct 20101 agtcttaatg gagtcacatt aattggagaa gccgtaaaaa cacagttcaa ttat tataag 20161 aaagttgatg gtgttgtcca acaattacct gaaacttact ttactcagag tagaaattta 20221 caagaattta aacccaggag tcaaatggaa attgatttct tagaattagc tatggatgaa 20281 ttcattgaac ggtataaatt agaaggctat gccttcgaac atatcgttta tggagatttt 20341 agtcatagtc agttaggtgg tttacatcta ctgattggac tagctaaacg ttttaaggaa 20401 tcaccttttg aattagaaga ttttattcct atggacagta cagttaaaaa ctatttcata 20461 acagatgcgc aaacaggttc atctaagtgt gtgtgttctg ttattgattt attacttgat 20521 gattttgttg aaataataaa atcccaagat ttatctgtag tttctaaggt tgtcaaagtg 20581 actattgact atacagaaat ttcatttatg ctttggtgta aagatggcca tgtagaaaca 20641 ttttacccaa aattacaatc tagtcaagcg tggcaaccgg gtgttgctat gcctaatctt 20701 tacaaaatgc aaagaatgct attagaaaag tgtgaccttc aaaattatgg tgatagtgca 20761 acattaccta aaggcataat gatgaatgtc gcaaaatata ctcaactgtg tcaatattta 20821 aacacattaa cattagctgt accctataat atgagagtta tacattttgg tgctggttct 20881 gataaaggag ttgcaccagg tacagctgtt ttaagacagt ggttgcctac gggtacgctg 20941 cttgtcgatt cagatcttaa tgactttgtc tctgatgcag attcaac ttt gattggtgat 21001 tgtgcaactg tacatacagc taataaatgg gatctcatta ttagtgatat gtacgaccct 21061 aagactaaaa atgttacaaa agaaaatgac tctaaagagg gttttttcac ttacatttgt 21121 gggtttatac aacaaaagct agctcttgga ggttccgtgg ctataaagat aacagaacat 21181 tcttggaatg ctgatcttta taagctcatg ggacacttcg catggtggac agcctttgtt 21241 actaatgtga atgcgtcatc atctgaagca tttttaattg gatgtaatta tcttggcaaa 21301 ccacgcgaac aaatagatgg ttatgtcatg catgcaaatt acatattttg gaggaataca 21361 aatccaattc agttgtcttc ctattcttta tttgacatga gtaaatttcc ccttaaatta 21421 aggggtactg ctgttatgtc tttaaaagaa ggtcaaatca atgatatgat tttatctctt 21481 cttagtaaag gtagacttat aattagagaa aacaacagag ttgttatttc tagtgatgtt 21541 cttgttaaca actaaacgaa caatgtttgt ttttcttgtt ttattgccac tagtctctag 21601 tcagtgtgtt aatcttacaa ccagaactca attaccccct gcatacacta attctttcac 21661 acgtggtgtt tattaccctg acaaagtttt cagatcctca gttttacatt caactcagga 21721 cttgttctta cctttctttt ccaatgttac ttggttccat gctatacatg tctctgggac 21781 caatggtact aagaggtttg ataaccctgt cctaccattt aatgatggtg tttattttgc 21841 ttccactgag aagtctaaca taataagagg ctggattttt ggtactactt tagattcgaa 21901 gacccagtcc ctacttattg ttaataacgc tactaatgtt gttattaaag tctgtgaatt 21961 tcaattttgt aatgatccat ttttgggtgt ttattaccac aaaaacaaca aaagttggat 22021 ggaaagtgag ttcagagttt attctagtgc gaataattgc acttttgaat atgtctctca 22081 gccttttctt atggaccttg aaggaaaaca gggtaatttc aaaaatctta gggaatttgt 22141 gtttaagaat attgatggtt attttaaaat atattctaag cacacgccta ttaatttagt 22201 gcgtgatctc cctcagggtt tttcggcttt agaaccattg gtagatttgc caataggtat 22261 taacatcact aggtttcaaa ctttacttgc tttacataga agttatttga ctcctggtga 22321 ttcttcttca ggttggacag ctggtgctgc agcttattat gtgggttatc ttcaacctag 22381 gacttttcta ttaaaatata atgaaaatgg aaccattaca gatgctgtag actgtgcact 22441 tgaccctctc tcagaaacaa agtgtacgtt gaaatccttc actgtagaaa aaggaatcta 22501 tcaaacttct aactttagag tccaaccaac agaatctatt gttagatttc ctaatattac 22561 aaacttgtgc ccttttggtg aagtttttaa cgccaccaga tttgcatctg tttatgcttg 22621 gaacaggaag agaatcagca actgtgttgc tg attattct gtcctatata attccgcatc 22681 attttccact tttaagtgtt atggagtgtc tcctactaaa ttaaatgatc tctgctttac 22741 taatgtctat gcagattcat ttgtaattag aggtgatgaa gtcagacaaa tcgctccagg 22801 gcaaactgga aagattgctg attataatta taaattacca gatgatttta caggctgcgt 22861 tatagcttgg aattctaaca atcttgattc taaggttggt ggtaattata attacctgta 22921 tagattgttt aggaagtcta atctcaaacc ttttgagaga gatatttcaa ctgaaatcta 22981 tcaggccggt agcacacctt gtaatggtgt tgaaggtttt aattgttact ttcctttaca 23041 atcatatggt ttccaaccca ctaatggtgt tggttaccaa ccatacagag tagtagtact 23101 ttcttttgaa cttctacatg caccagcaac tgtttgtgga cctaaaaagt ctactaattt 23161 ggttaaaaac aaatgtgtca atttcaactt caatggttta acaggcacag gtgttcttac 23221 tgagtctaac aaaaagtttc tgcctttcca acaatttggc agagacattg ctgacactac 23281 tgatgctgtc cgtgatccac agacacttga gattcttgac attacaccat gttcttttgg 23341 tggtgtcagt gttataacac caggaacaaa tacttctaac caggttgctg ttctttatca 23401 ggatgttaac tgcacagaag tccctgttgc tattcatgca gatcaactta ctcctacttg 23461 gcgtgtttat tctacaggtt ctaat gtttt tcaaacacgt gcaggctgtt taataggggc 23521 tgaacatgtc aacaactcat atgagtgtga catacccatt ggtgcaggta tatgcgctag 23581 ttatcagact cagactaatt ctcctcggcg ggcacgtagt gtagctagtc aatccatcat 23641 tgcctacact atgtcacttg gtgcagaaaa ttcagttgct tactctaata actctattgc 23701 catacccaca aattttacta ttagtgttac cacagaaatt ctaccagtgt ctatgaccaa 23761 gacatcagta gattgtacaa tgtacatttg tggtgattca actgaatgca gcaatctttt 23821 gttgcaatat ggcagttttt gtacacaatt aaaccgtgct ttaactggaa tagctgttga 23881 acaagacaaa aacacccaag aagtttttgc acaagtcaaa caaatttaca aaacaccacc 23941 aattaaagat tttggtggtt ttaatttttc acaaatatta ccagatccat caaaaccaag 24001 caagaggtca tttattgaag atctactttt caacaaagtg acacttgcag atgctggctt 24061 catcaaacaa tatggtgatt gccttggtga tattgctgct agagacctca tttgtgcaca 24121 aaagtttaac ggccttactg ttttgccacc tttgctcaca gatgaaatga ttgctcaata 24181 cacttctgca ctgttagcgg gtacaatcac ttctggttgg acctttggtg caggtgctgc 24241 attacaaata ccatttgcta tgcaaatggc ttataggttt aatggtattg gagttacaca 24301 gaatgttctc tatgagaa cc aaaaattgat tgccaaccaa tttaatagtg ctattggcaa 24361 aattcaagac tcactttctt ccacagcaag tgcacttgga aaacttcaag atgtggtcaa 24421 ccaaaatgca caagctttaa acacgcttgt taaacaactt agctccaatt ttggtgcaat 24481 ttcaagtgtt ttaaatgata tcctttcacg tcttgacaaa gttgaggctg aagtgcaaat 24541 tgataggttg atcacaggca gacttcaaag tttgcagaca tatgtgactc aacaattaat 24601 tagagctgca gaaatcagag cttctgctaa tcttgctgct actaaaatgt cagagtgtgt 24661 acttggacaa tcaaaaagag ttgatttttg tggaaagggc tatcatctta tgtccttccc 24721 tcagtcagca cctcatggtg tagtcttctt gcatgtgact tatgtccctg cacaagaaaa 24781 gaacttcaca actgctcctg ccatttgtca tgatggaaaa gcacactttc ctcgtgaagg 24841 tgtctttgtt tcaaatggca cacactggtt tgtaacacaa aggaattttt atgaaccaca 24901 aatcattact acagacaaca catttgtgtc tggtaactgt gatgttgtaa taggaattgt 24961 caacaacaca gtttatgatc ctttgcaacc tgaattagac tcattcaagg aggagttaga 25021 taaatatttt aagaatcata catcaccaga tgttgattta ggtgacatct ctggcattaa 25081 tgcttcagtt gtaaacattc aaaaagaaat tgaccgcctc aatgaggttg ccaagaattt 25141 aaatgaatct ctcatcgatc tccaagaact gagcagtata taaaatggcc 25201 atggtacatt tggctaggtt ttatagctgg cttgattgcc atagtaatgg tgacaattat 25261 gctttgctgt atgaccagtt gctgtagttg tctcaagggc tgttgttctt gtggatcctg 25321 ctgcaaattt gatgaagacg actctgagcc agtgctcaaa ggagtcaaat tacattacac 25381 ataaacgaac ttatggattt gtttatgaga atcttcacaa ttggaactgt aactttgaag 25441 caaggtgaaa tcaaggatgc tactccttca gattttgttc gcgctactgc aacgataccg 25501 atacaagcct cactcccttt cggatggctt attgttggcg ttgcacttct tgctgttttt 25561 cagagcgctt ccaaaatcat tggaaagtat aaccctcaaa aagagatggc aactagcact ctccaagggt 25621 gttcactttg tttgcaactt gctgttgttg tttgtaacag tttactcaca ccttttgctc 25681 gttgctgctg gccttgaagc cccttttctc tatctttatg ctttagtcta cttcttgcag agtataaact ttgtaagaat aataatgagg ctttggcttt gctggaaatg ccgttccaaa 25801 aacccattac tttatgatgc caactatttt ctttgctggc atactaattg ttacgactat 25861 tgtatacctt acaatagtgt aacttcttca attgtcatta cttcaggtga tggcacaaca 25921 agtcctattt ctgaacatga ctaccagatt ggtggttata ctgaaaaatg ggaatctgga 25741 25981 gta aaagact gtgttgtatt acacagttac ttcacttcag actattacca gctgtactca 26041 actcaattga gtacagacac tggtgttgaa catgttacct tcttcatcta caataaaatt 26101 gttgatgagc ctgaagaaca tgtccaaatt cacacaatcg acggttcatc cggagttgtt 26161 aatccagtaa tggaaccaat ttatgatgaa ccgacgacga ctactagcgt gcctttgtaa 26221 gcacaagctg atgagtacga acttatgtac tcattcgttt cggaagagac aggtacgtta 26281 atagttaata gcgtacttct ttttcttgct ttcgtggtat tcttgctagt tacactagcc 26341 atccttactg cgcttcgatt gtgtgcgtac tgctgcaata ttgttaacgt gagtcttgta 26401 aaaccttctt tttacgttta ctctcgtgtt aaaaatctga attcttctag agttcctgat 26461 cttctggtct aaacgaacta aatattatat tagtttttct gtttggaact ttaattttag 26521 ccatggcaga ttccaacggt actattaccg ttgaagagct taaaaagctc cttgaacaat 26581 ggaacctagt aataggtttc ctattcctta catggatttg tcttctacaa tttgcctatg 26641 ccaacaggaa taggtttttg tatataatta agttaatttt cctctggctg ttatggccag 26701 taactttagc ttgttttgtg cttgctgctg tttacagaat aaattggatc accggtggaa 26761 ttgctatcgc aatggcttgt cttgtaggct tgatgtggct cagctacttc attgcttctt 2 6821 tcagactgtt tgcgcgtacg cgttccatgt ggtcattcaa tccagaaact aacattcttc 26881 tcaacgtgcc actccatggc actattctga ccagaccgct tctagaaagt gaactcgtaa 26941 tcggagctgt gatccttcgt ggacatcttc gtattgctgg acaccatcta ggacgctgtg 27001 acatcaagga cctgcctaaa gaaatcactg ttgctacatc acgaacgctt tcttattaca 27061 aattgggagc ttcgcagcgt gtagcaggtg actcaggttt tgctgcatac agtcgctaca 27121 ggattggcaa ctataaatta aacacagacc attccagtag cagtgacaat attgctttgc 27181 ttgtacagta agtgacaaca gatgtttcat ctcgttgact ttcaggttac tatagcagag 27241 atattactaa ttattatgag gacttttaaa gtttccattt ggaatcttga ttacatcata 27301 aacctcataa ttaaaaattt atctaagtca ctaactgaga ataaatattc tcaattagat 27361 gaagagcaac caatggagat tgattaaacg aacatgaaaa ttattctttt cttggcactg 27421 ataacactcg ctacttgtga gctttatcac taccaagagt gtgttagagg tacaacagta 27481 cttttaaaag aaccttgctc ttctggaaca tacgagggca attcaccatt tcatcctcta 27541 gctgataaca aatttgcact gacttgcttt agcactcaat ttgcttttgc ttgtcctgac 27601 ggcgtaaaac acgtctatca gttacgtgcc agatcagttt cacctaaact gttc atcaga 27661 caagaggaag ttcaagaact ttactctcca aatagtgttt atttttctta ttgttgcggc tattagagta ggagctagaa aatcagcacc 27721 ataacacttt gcttcacact caaaagaaag acagaatgat tgaactttca ttaattgact 27781 tctatttgtg ctttttagcc tttctgctat tccttgtttt aattatgctt attatctttt 27841 ggttctcact tgaactgcaa gatcataatg aaacttgtca cgcctaaacg aacatgaaat 27901 ttcttgtttt cttaggaatc atcacaactg tagctgcatt tcaccaagaa tgtagtttac 27961 agtcatgtac tcaacatcaa ccatatgtag ttgatgaccc gtgtcctatt cacttctatt 28021 ctaaatggta tttaattgaa ttgtgcgtgg 28081 atgaggctgg ttctaaatca cccattcagt acatcgatat cggtaattat acagtttcct 28141 gtttaccttt tacaattaat tgccaggaac ctaaattggg tagtcttgta gtgcgttgtt 28201 cgttctatga agacttttta gagtatcatg acgttcgtgt tgttttagat ttcatctaaa 28261 cgaacaaact aaaatgtctg ataatggacc ccaaaatcag cgaaatgcac cccgcattac 28321 gtttggtgga ccctcagatt caactggcag taaccagaat ggagaacgca gtggggcgcg 28381 atcaaaacaa cgtcggcccc aaggtttacc caataatact gcgtcttggt tcaccgctct 28441 cactcaacat ggcaaggaag accttaaatt ccctcgagga caag gcgttc caattaacac 28501 caatagcagt ccagatgacc aaattggcta ctaccgaaga gctaccagac gaattcgtgg 28561 tggtgacggt aaaatgaaag atctcagtcc aagatggtat ttctactacc taggaactgg 28621 gccagaagct ggacttccct atggtgctaa caaagacggc atcatatggg ttgcaactga 28681 gggagccttg aatacaccaa aagatcacat tggcacccgc aatcctgcta acaatgctgc 28741 aatcgtgcta caacttcctc aaggaacaac attgccaaaa ggcttctacg cagaagggag 28801 cagaggcggc agtcaagcct cttctcgttc ctcatcacgt agtcgcaaca gttcaagaaa 28861 ttcaactcca ggcagcagta ggggaacttc tcctgctaga atggctggca atggcggtga 28921 tgctgctctt gctttgctgc tgcttgacag attgaaccag cttgagagca aaatgtctgg 28981 taaaggccaa caacaacaag gccaaactgt cactaagaaa tctgctgctg aggcttctaa 29041 gaagcctcgg caaaaacgta ctgccactaa agcatacaat gtaacacaag ctttcggcag 29101 acgtggtcca gaacaaaccc aaggaaattt tggggaccag gaactaatca gacaaggaac 29161 tgattacaaa cattggccgc aaattgcaca atttgccccc agcgcttcag cgttcttcgg 29221 aatgtcgcgc attggcatgg aagtcacacc ttcgggaacg tggttgacct acacaggtgc 29281 catcaaattg gatgacaaag atccaaattt caaagat caa gtcattttgc tgaataagca 29341 tattgacgca tacaaaacat tcccaccaac agagcctaaa aaggacaaaa agaagaaggc 29401 tgatgaaact caagccttac cgcagagaca gaagaaacag caaactgtga ctcttcttcc 29461 tgctgcagat ttggatgatt tctccaaaca attgcaacaa tccatgagca gtgctgactc 29521 aactcaggcc taaactcatg cagaccacac aaggcagatg ggctatataa acgttttcgc 29581 ttttccgttt acgatatata gtctactctt gtgcagaatg aattctcgta actacatagc 29641 acaagtagat gtagttaact ttaatctcac atagcaatct ttaatcagtg tgtaacatta 29701 gggaggactt gaaagagcca ccacattttc accgaggcca cgcggagtac gatcgagtgt 29761 acagtgaaca atgctaggga gagctgccta tatggaagag ccctaatgtg taaaattaat 29821 tttagtagtg ctatccccat gtgattttaa tagcttctta ggagaatgac aaaaaaaaaa 29881 aaaaaaaaaa aaaaaaaaa SARS-CoV-2 Wuhan Seafood Market Pneumonia Virus Isolate Wuhan-Hu-1 Genome Sequence (GenBank: MN908947.3; January 23, 2020)-amino acid translation 2 MESLVPGFNEKTHVQLSLPVLQVRDVLVRGFGDSVEEVLSEARQHLKDGTCGLVEVEKGVLPQLEQPYVFIKRSDARTAPHGHVMVELVAELEGIQYGRSGETLGVLVPHVGEIPVAYRKVLLRKNGNKGAGGHSYGADLKSFDLGDELGTDPYEDFQEN WNTKHSSGVTRELMRELNGGAYTRYVDNNFCGPDGYPLECIKDLLARAGKASCTLSEQLDFIDTKRGVYCCREHEHEIAWYTERSEKSYELQTPFEIKLAKKFDTFNGECPNFVFPLNSIIKTIQPRVEKKKLDGFMGRIRSVYPVASPNECNQMCLSTLMKCDHCGETSWQTGDFVKATCEFCGTENLTKEGATTCGYLPQNAVVKIYCPACHNSEVGPEHSLAEYHNESGLKTILRKGGRTIAFGGCVFSYVGCHNKCAYWVPRASANIGCNHTGVVGEGSEGLNDNL LEILQKEKVNINIVGDFKLNEEIAIILASFSASTSAFVETVKGLDYKAFKQIVESCGNFKVTKGKAKKGAWNIGEQKSILSPLYAFASEAARVVRSIFSRTLETAQNSVRVLQKAAITILDGISQYSLRLIDAMMFTSDLATNNLVVMAYITGGVVQLTSQWLTNIFGTVYEKLKPVLDWLEEKFKEGVEFLRDGWEIVKFISTCACEIVGGQIVTCAKEIKESVQTFFKLVNKFLALCADSIIIGGAKLKALNLGETFVTHSKGLYRKCVKSREETGLLMPLKAPKEIIFLEGETLPTEVLTEEVVLKTGDLQPLEQPTSEAVEAPLVGTPVCINGLMLLEIKDTEKYCALAPNMMVTNNTFTLKGGAPTKVTFGDDTVIEVQGYKSVNITFELDERIDKVLNEKCSAYTVELGTEVNEFACVVADAVIKTLQPVSELLTPLGIDLDEWSMATYYLFDESGEFKLASHMYCSFYPPDEDEEEGDCEEEEFEPSTQYEYGTEDDYQGKPLEFGATSAALQPEEEQEEDW LDDDSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIEVNSFSGYLKLTDNVYIKNADIVEEAKKVKPTVVVNAANVYLKHGGGVAGALNKATNNAMQVESDDYIATNGPLKVGGSCVLSGHNLAKHCLHVVGPNVNKGEDIQLLKSAYENFNQHEVLLAPLLSAGIFGADPIHSLRVCVDTVRTNVYLAVFDKNLYDKLVSSFLEMKSEKQVEQKIAEIPKEEVKPFITESKPSVEQRKQDDKKIKACVEEVTTTLEETKFLTENLLLYIDINGNLHPDSATLVSDIDITFLKKDAPYIVGDVVQEGVLTAVVIPTKKAGGTTEMLAKALRKVPTDNYITTYPGQGLNGYTVEEAKTVLKKCKSAFYILPSIISNEKQEILGTVSWNLREMLAHAEETRKLMPVCVETKAIVSTIQRKYKGIKIQEGVVDYGARFYFYTSKTTVASLINTLNDLNETLVTMPLGYVTHGLNLEEAARYMRSLKVPATVSVSSPDAVTAYNGYLTSSSKTPEEHFIETISLAGSYKDWSYSGQSTQLGIEFLKRGDKSVYYTSNPTTFHLDGEVITFDNLKTLLSLREVRTIKVFTTVDNINLHTQVVDMSMTYGQQFGPTYLDGADVTKIKPHNSHEGKTFYVLPNDDTLRVEAFEYYHTTDPSFLGRYMSALNHTKKWKYPQVNGLTSIKWADNNCYLATALLTLQQIELKFNPPALQDAYYRARAGEAANFCALILAYCNKTVGELGDVRETMSYLFQHANLDSCKRVLNVVCKTCGQQQTTLKGVEAVMYMGTLSYEQFKKGVQIPCTCGKQATKYLVQQESPFVMMSAPPAQYELKHGTFTCASEYTGNYQCGHYKHITSKETLYCIDGALLTKSSEYKGPITDVFYKENSYTTTIKPVTYKLDGVVCTEIDPKLDNYYKKDNSYFTEQPIDLVPNQPYPNASFDNFKFVCDNIKFADDLNQLTGYKKPASRELKVTFFPDLNGDVVAIDYKHYTPSF KKGAKLLHKPIVWHVNNATNKATYKPNTWCIRCLWSTKPVETSNSFDVLKSEDAQGMDNLACEDLKPVSEEVVENPTIQKDVLECNVKTTEVVGDIILKPANNSLKITEEVGHTDLMAAYVDNSSLTIKKPNELSRVLGLKTLATHGLAAVNSVPWDTIANYAKPFLNKVVSTTTNIVTRCLNRVCTNYMPYFFTLLLQLCTFTRSTNSRIKASMPTTIAKNTVKSVGKFCLEASFNYLKSPNFSKLINIIIWFLLLSVCLGSLIYSTAALGVLMSNLGMPSYCTGYREGYLNSTNVTIATYCTGSIPCSVCLSGLDSLDTYPSLETIQITISSFKWDLTAFGLVAEWFLAYILFTRFFYVLGLAAIMQLFFSYFAVHFISNSWLMWLIINLVQMAPISAMVRMYIFFASFYYVWKSYVHVVDGCNSSTCMMCYKRNRATRVECTTIVNGVRRSFYVYANGGKGFCKLHNWNCVNCDTFCAGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVTVKNGSIHLYFDKAGQKTYERHSLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCEESSAKSASVYYSQLMCQPILLLDQALVSDVGDSAEVAVKMFDAYVNTFSSTFNVPMEKLKTLVATAEAELAKNVSLDNVLSTFISAARQGFVDSDVETKDVVECLKLSHQSDIEVTGDSCNNYMLTYNKVENMTPRDLGACIDCSARHINAQVAKSHNIALIWNVKDFMSLSEQLRKQIRSAAKKNNLPFKLTCATTRQVVNVVTTKIALKGGKIVNNWLKQLIKVTLVFLFVAAIFYLITPVHVMSKHTDFSSEIIGYKAIDGGVTRDIASTDTCFANKHADFDTWFSQRGGSYTNDKACPLIAAVITREVGFVVPGLPGTILRTTNGDFLHFLPRVFSAVGNICYTPSKLIEYTDFATSACVLAAECTIFKDASGKPVPYCYDTNVLEGSVAYESLRPDTRYVLMDGSIIQFPNTYLEGSVRVVTTF DSEYCRHGTCERSEAGVCVSTSGRWVLNNDYYRSLPGVFCGVDAVNLLTNMFTPLIQPIGALDISASIVAGGIVAIVVTCLAYYFMRFRRAFGEYSHVVAFNTLLFLMSFTVLCLTPVYSFLPGVYSVIYLYLTFYLTNDVSFLAHIQWMVMFTPLVPFWITIAYIICISTKHFYWFFSNYLKRRVVFNGVSFSTFEEAALCTFLLNKEMYLKLRSDVLLPLTQYNRYLALYNKYKYFSGAMDTTSYREAACCHLAKALNDFSNSGSDVLYQPPQTSITSAVLQSGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIRKSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGNFYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQCSGVTFQSAVKRTIKGTHHWLLLTILTSLLVLVQSTQWSLFFFLYENAFLPFAMGIIAMSAFAMMFVKHKHAFLCLFLLPSLATVAYFNMVYMPASWVMRIMTWLDMVDTSLSGFKLKDCVMYASAVVLLILMTARTVYDDGARRVWTLMNVLTLVYKVYYGNALDQAISMWALIISVTSNYSGVVTTVMFLARGIVFMCVEYCPIFFITGNTLQCIMLVYCFLGYFCTCYFGLFCLLNRYFRLTLGVYDYLVSTQEFRYMNSQGLLPPKNSIDAFKLNIKLLGVGGKPCIKVATVQSKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRATLQAIASEFSSLPSYAAFATAQEAYEQAVANGDSEVVLKK LKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKRAKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVIPDYNTYKNTCDGTTFTYASALWEIQQVVDADSKIVQLSEISMDNSPNLAWPLIVTALRANSAVKLQNNELSPVALRQMSCAAGTTQTACTDDNALAYYNTTKGGRFVLALLSDLQDLKWARFPKSDGTGTIYTELEPPCRFVTDTPKGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQAGNATEVPANSTVLSFCAFAVDAAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCHIDHPNPKGFCDLKGKYVQIPTTCANDPVGFTLKNTVCTVCGMWKGYGCSCDQLREPMLQSADAQSFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNDKVAGFAKFLKTNCCRFQEKDEDDNLIDSYFVVKRHTFSNYQHEETIYNLLKDCPAVAKHDFFKFRIDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDFVENPDILRVYANLGERVRQALLKTVQFCDAMRNAGIVGVLTLDNQDLNGNWYDFGDFIQTTPGSGVPVV Surface Glycoprotein [SARS-CoV-2 Wuhan Seafood Market Pneumonia Virus]: GenBank: QHD43416.1; January 23, 2020 3 mfvflvllpl vssqcvnltt rtqlppaytn sftrgvyypd kvfrssvlhs tqdlflpffs 61 nvtwfhaihv sgtngtkrfd npvlpfndgv yfasteksni irgwifgttl dsktqslliv 121 nnatnvvikv cefqfcndpf lgvyyhknnk swmesefrvy ssannctfey vsqpflmdle181 gkqgnfknlr efvfknidgy fkiyskhtpi nlvrdlpqgf saleplvdlp iginitrfqt 241 llalhrsylt pgdsssgwta gaaayyvgyl qprtfllkyn engtitdavd caldplsetk 301 ctlksftvek giyqtsnfrv qptesivrfp nitnlcpfge vfnatrfasv yawnrkrisn 361 cvadysvlyn sasfstfkcy gvsptklndl cftnvyadsf virgdevrqi apgqtgkiad 421 ynyklpddft gcviawnsnn ldskvggnyn ylyrlfrksn lkpferdist eiyqagstpc 481 ngvegfncyf plqsygfqpt ngvgyqpyrv vvlsfellha patvcgpkks tnlvknkcvn 541 fnfngltgtg vltesnkkfl pfqqfgrdia dttdavrdpq tleilditpc sfggvsvitp 601 gtntsnqvav lyqdvnctev pvaihadqlt ptwrvystgs nvfqtragcl igaehvnnsy 661 ecdipigagi casyqtqtns prrarsvasq siiaytmslg aensvaysnn siaiptnfti 721 svtteilpvs mtktsvdctm yicgdstecs nlllqygsfc tqlnraltgi aveqdkntqe 781 vfaqvkqiyk tppikdfggf nfsqilpdps kpskrsfied llfnkvtlad agfikqygdc 841 lgdiaardli caqkfngltv lpplltdemi aqytsallag titsgwtfga gaalqipfam 901 qmayrfngig vtqnvlyenq klianqfnsa igkiqdslss tasalgklqd vvnqnaqaln 961 tlvkqlssnf gaissvlndi lsrldkveae vqidrlitgr lqslqtyvtq qliraaeira 1021 sanlaatkms ecvlgqskrv dfcgkgyhlm sfpqsaphgv vflhvtyvpa qeknfttapa 1081 ichdgkahfp regvfvsngt hwfvtqrnfy epqiittdnt fvsgncdvvi givnntvydp 1141 lqpeldsfke eldkyfknht spdvdlgdis ginasvvniq keidrlneva knlneslidl 1201 qelgkyeqyi kwpwyiwlgf iagliaivmv timlccmtsc csclkgccsc gscckfdedd 1261 sepvlkgvkl hyt Surface glycoprotein RBD [SARS-CoV-2 Wuhan seafood market pneumonia virus]; GenBank: QHD43416.1; January 23, 2020 4 nitnlcpfgevfnatrfasvyawnrkrisncvadysvlynsasfstfkcygvsptklndlcftnvyadsfvirgdevrqiapgqtgkiadynyklpddftgcviawnsnnldskvggnynylyrlfrksnlkpferdisteiyqagstpcngnvegfncyfplqsygfqptngvgyqpyrvvvlsfellhapatvcgpkkltgstnlv Receptor Binding Motif (RBM) in Surface Glycoprotein RBD [SARS-CoV-2 Wuhan Seafood Market Pneumonia Virus]; GenBank: QHD43416.1; 23 Jan 2020 5 Nsnnldskvggnynylyrlfrksnlkpferdisteiyqagstpcngvegfncyfplqsygfqptngvgyqpy SARS-CoV-2 CH1-CH3 LS G1m17 IgHG1*01 (aa) 6 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK SARS-CoV-2 CH1-CH3 LS, ALE G1m17 IgHG1*01 (aa) 7 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK SARS-CoV-2 CL IgLC*01 (aa) 8 GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS SARS-CoV-2 CL (CK) k1m3 IgKC*01 (aa) 9 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC linker (aa) 10 GSTSGSGKPGSGEGSTKG linker (aa) 11 GSGKPGSGEG linker (aa) 12 GKPGSGEG linker (aa) 13 SGKPGSGE linker (aa) 14 BPXXXZ, where each X is independently glycine (G) or serine (S), B is a positively charged amino acid and Z is glycine (G) or a negatively charged amino acid linker (aa) 15 (GxS)y, where x is 1-10 and y is 1-10 linker (aa) 16 GGGGSGGGGSGGGGS linker (aa) 17 GGGGSGGGGSGGGGSGGGGSGGGGS GGGGSGGGGSGGGGSGGGGSGGGGS linker (aa) 18 GSTSGGGSGGGSGGGGSS linker (aa) 19 EGKSSGSGSESKVD linker (aa) 20 KESGSVSSEQLAQFRSLD linker (aa) twenty one GGGGS SARS-CoV-2 S2X16-v1 mAb VH (aa) twenty two EVQLVQSGAEVKKPGASVKVSCKAS GYIFTDHY MHWVRQAPGQGLEWMGW INPNSGGT NYAQKFQGRVTMTRDTSINTAYMELSRLRSDDTAVHYC ARDRSRFRFFSPDFDY WGQGTLVTVSS SARS-CoV-2 S2X16-v1 mAb CDRH1 (aa) twenty three GYIFTDHY SARS-CoV-2 S2X16-v1 mAb CDRH2 (aa) twenty four INPNSGGT SARS-CoV-2 S2X16-v1 mAb CDRH3 (aa) 25 ARDRSRFRFFSPDFDY SARS-CoV-2 S2X16-v1 mAb VL (aa) 26 EIVLTQSPLSLPVTPGEPASISCRSS QSLLHSNGYNY LDWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPPT FGQGTKVEIK SARS-CoV-2 S2X16-v1 mAb CDRL1 (aa) 27 QSLLHSNGYNY SARS-CoV-2 S2X16-v1 mAb CDRL2 (aa) 28 LGS SARS-CoV-2 S2X16-v1 mAb CDRL3 (aa) 29 MQALQTPPT SARS-CoV-2 S2X16-v1 mAb VH (nt) 30 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACATCTTCACCGACCACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTAACAGTGGTGGCACA AACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAACACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGCATTACTGT GCGAGAGATCGGTCACGATTTCGATTTTTCTCCCCCGACTTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X16-v1 mAb VL (nt) 31 GAAATTGTGCTGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGT CAGAGCCTCCTGCATAGTAATGGATACAACTAT TTGGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTAT TTGGGTTCT AATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGCTCAGGCACAGATTTCACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGC ATGCAAGCTCTACAAACTCCTCCAACG TTCGGCCAAGGGACCAAGGTGGAAATCAAAC SARS-CoV-2 S2X28-v1 mAb VH (aa) 32 EVQLVESGGGVVQPGRSLRLSCAAS GFTFSTYA MHWVRQAPGKGLEWVAV ILSDGSNK YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDRSPLVGFGDNYGMDV WGQGTTVTVSS SARS-CoV-2 S2X28-v1 mAb CDRH1 (aa) 33 GFTFSTYA SARS-CoV-2 S2X28-v1 mAb CDRH2 (aa) 34 ILSDGSNK SARS-CoV-2 S2X28-v1 mAb CDRH3 (aa) 35 ARDRSPLVGFGDNYGMDV SARS-CoV-2 S2X28-v1 mAb VL (aa) 36 SYELTQPPSVSVSPGQTARITCSGD ALPKKY AYWYQQKSGQAPVLVIY EDS KRPSGIPERFSGSSSGTMATLTISGAQVEDEADYYC SSTDSSGNQGVFGGGTKLTVL SARS-CoV-2 S2X28-v1 mAb CDRL1 (aa) 37 ALPKKY SARS-CoV-2 S2X28-v1 mAb CDRL2 (aa) 38 EDS SARS-CoV-2 S2X28-v1 mAb CDRL3 (aa) 39 SSTDSSGNQGV SARS-CoV-2 S2X28-v1 mAb VH (nt) 40 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCACCTTCAGTACCTATGCT ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTAGAGTGGGTGGCAGTT ATATTATCTGATGGAAGTAATAAA TATTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGT GCGAGAGATCGAAGTCCCCTCGTGGGATTCGGGGACAACTATGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2X28-v1 mAb VL (nt) 41 TCCTATGAGCTGACACAGCCACCCTCGGTGTCAGTGTCCCCAGGACAAACGGCCAGGATCACCTGCTCTGGAGAT GCATTGCCAAAAAAATAT GCTTATTGGTACCAGCAGAAGTCAGGCCAGGCCCCTGTGCTGGTCATCTAT GAGGACAGC AAACGACCCTCCGGGATCCCTGAGAGATTCTCTGGCTCCAGCTCAGGGACAATGGCCACCTTGACTATCAGTGGGGCCCAGGTGGAGGATGAAGCTGACTACTACTGT TCCTCAACAGACAGCAGTGGTAATCAAGGGGTA TTCGGCGGAGGGACCAAGCTGACCGTCCTAG SARS-CoV-2 S2X30-v1 mAb VH (aa) 42 EVQLVQSGAEVKKPGSSVKVSCKAS GGTFGSYT ISWVRQAPGQGLEWMGR IIPILSIP NYAQKFQGRVTFTADKSTSTAYMELSSLRSEDTAVYYC ARGGGGTHAVPHYYFDSWGQGTLVTVSS SARS-CoV-2 S2X30-v1 mAb CDRH1 (aa) 43 GGTFGSYT SARS-CoV-2 S2X30-v1 mAb CDRH2 (aa) 44 IIPILSIP SARS-CoV-2 S2X30-v1 mAb CDRH3 (aa) 45 ARGGGGTHAVPHYYFDS SARS-CoV-2 S2X30-v1 mAb VL (aa) 46 EIVMMQSPATLSVSPGERATLSCRAS QSVSSN LAWYQHKPGQAPRLLIY GAS TRATGIPARFSGSGSGTEFTLTISSMQSEDFAVYYCQQYNNWPFTFGGGTKVEIK SARS-CoV-2 S2X30-v1 mAb CDRL1 (aa) 47 QSVSSN SARS-CoV-2 S2X30-v1 mAb CDRL2 (aa) 48 GAS SARS-CoV-2 S2X30-v1 mAb CDRL3 (aa) 49 QQYNNWPFT SARS-CoV-2 S2X30-v1 mAb VH (nt) 50 GAGGTGCAGCTGGTGCAATCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCT GGAGGCACCTTCGGCAGCTATACT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAAGG ATCATCCCTATCCTTAGTATACCA AACTACGCACAGAAGTTCCAGGGCAGAGTCACGTTTACCGCGGACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGT GCGAGAGGAGGGGGTGGGACCCACGCAGTTCCCCACTACTACTTTGACTCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X30-v1 mAb VL (nt) 51 GAAATAGTGATGATGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGT CAGAGTGTTAGCAGCAAC TTAGCCTGGTACCAGCATAAACCTGGCCAGGCTCCCAGGCTCCTCATCTAT GGTGCATCC ACCAGGGCCACTGGTATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCATGCAGTCTGAAGATTTTGCAGTTTATTACTGT CAGCAGTATAATAACTGGCCTTTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAAC SARS-CoV-2 S2X47-v1 mAb VH (aa) 52 QVQLQESGPGLVKPSQTLSLTCTVS GGSISS R SYY WSWIRQPAGKGLEWIGR IYTSG N T NYNPSLRSRVTISVDTSKNQFSLKLGSVTAADTAVYYC ARERIIGTAHVGGWFDPWGQGTLVTVSS SARS-CoV-2 S2X47-v1 mAb CDRH1 (aa) 53 GGSISS RSYY SARS-CoV-2 S2X47-v1 mAb CDRH2 (aa) 54 IYTSG NT SARS-CoV-2 S2X47-v1 mAb CDRH3 (aa) 55 ARERIIGTAHVGGWFDP SARS-CoV-2 S2X47-v1 mAb VL (aa) 56 QTVVTQPPSASGTPGQRVTISCSGS SSNIGSDT VNWYLQLPGTAPKLLIY TNN QRPSGVPDRFSGSKSGTSASLAISGLQSEDEANYYC AAWDDSLNGWVFGGGTKLTVL SARS-CoV-2 S2X47-v1 mAb CDRL1 (aa) 57 SSNIGSDT SARS-CoV-2 S2X47-v1 mAb CDRL2 (aa) 58 TNN SARS-CoV-2 S2X47-v1 mAb CDRL3 (aa) 59 AAWDDSLNGWV SARS-CoV-2 S2X47-v1 mAb VH (nt) 60 CAGGTGCAGCTACAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTCACCTGCACTGTCTCT GGTGGCTCCATCAGCAGTCGAAGTTACTAC TGGAGCTGGATCCGGCAGCCCGCCGGGAAGGGACTGGAGTGGATTGGGCGT ATCTATACCAGTGGCAACACC AACTACAACCCCTCCCTCAGGAGTCGAGTCACCATATCAGTGGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGGGCTCTGTGACCGCCGCAGACACGGCCGTGTATTATTGT GCGAGAGAGCGTATAATTGGAACCGCGCACGTGGGTGGGTGGTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X47-v1 mAb VL (nt) 61 CAGACTGTGGTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGTTCTGGAAGC AGCTCCAACATCGGAAGTGATACT GTAAACTGGTACCTGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTAT ACTAATAAT CAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAGGCTAATTATTACTGT GCAGCATGGGATGACAGCCTGAATGGTTGGGTG TTCGGCGGAGGGACCAAGCTGACCGTCCTAG SARS-CoV-2 S2X55-v1 mAb VH (aa) 62 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY MHWVRQAPGQGLEWMGW INPNSGAT NFAQKFQGRVTMTRDRSISTAYMELRSLRSDDTAVYYCARDLGDSRLSGWFDPWGQGTLVTVSS SARS-CoV-2 S2X55-v1 mAb CDRH1 (aa) 63 GYTFTGYY SARS-CoV-2 S2X55-v1 mAb CDRH2 (aa) 64 INPNSGAT SARS-CoV-2 S2X55-v1 mAb CDRH3 (aa) 65 ARDLGDSRLSGWFDP SARS-CoV-2 S2X55-v1 mAb VL (aa) 66 QSALTQPASVSGSPGQSITISCTGT SSDVGSYNL VSWYQQHPGKAPKLMIY EGS KRPSGVSYRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGSSTWVFGGGTKLTVL SARS-CoV-2 S2X55-v1 mAb CDRL1 (aa) 67 SSDVGSYNL SARS-CoV-2 S2X55-v1 mAb CDRL2 (aa) 68 EGS SARS-CoV-2 S2X55-v1 mAb CDRL3 (aa) 69 CSYAGSSTWV SARS-CoV-2 S2X55-v1 mAb VH (nt) 70 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTAACAGTGGTGCCACA AACTTTGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACAGGTCCATCAGCACAGCCTACATGGAGTTGAGAAGCCTGAGATCTGACGACACGGCCGTTTATTACTGT GCGAGAGATCTCGGGGATAGCAGGTTGAGTGGCTGGTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X55-v1 mAb VL (nt) 71 CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACC AGCAGTGATGTTGGGAGTTATAACCTT GTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTAT GAGGGCAGT AAGCGGCCCTCAGGGGTTTCTTATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGC TGCTCATATGCAGGTAGTAGCACTTGGGTG TTCGGCGGAGGGACCAAGCTGACCGTCCTAG SARS-CoV-2 S2X55-v2 mAb VH (aa) 72 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY MHWVRQAPGQGLEWMGW INPNSGAT NFAQKFQGRVTMTRDRSISTAYMELRSLRSDDTAVYYC ARDLGDSRLSGWFDP WGQGTLVTVSS SARS-CoV-2 S2X55-v2 mAb VH (nt) 73 CAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTAACAGTGGTGCCACA AACTTTGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACAGGTCCATCAGCACAGCCTACATGGAGTTGAGAAGCCTGAGATCTGACGACACGGCCGTTTATTACTGT GCGAGAGATCTCGGGGATAGCAGGTTGAGTGGCTGGTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X56-v1 mAb VH (aa) 74 QVQLVQSGAEVKKPGSSVKVSCKAS GGTFGSYT ISWVRQAPGQGLEWMGR IIPILSIP NYAQKFQGRVTFTADKSTSTAYMELSSLRSEDTAVYYC ARGGGGTHAVPHYYFDS WGQGTLVTVSS SARS-CoV-2 S2X56-v1 mAb CDRH1 (aa) 75 GGTFGSYT SARS-CoV-2 S2X56-v1 mAb CDRH2 (aa) 76 IIPILSIP SARS-CoV-2 S2X56-v1 mAb CDRH3 (aa) 77 ARGGGGTHAVPHYYFDS SARS-CoV-2 S2X56-v1 mAb VL (aa) 78 QTVLTQPASVSGSPGQSITISCTGT SSDVGSYNL VSWYQQHPGKAPKLMIY EGS KRPSGV SNRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGSSTHVFGTGTKVIVL SARS-CoV-2 S2X56-v1 mAb CDRL1 (aa) 79 SSDVGSYNL SARS-CoV-2 S2X56-v1 mAb CDRL2 (aa) 80 EGS SARS-CoV-2 S2X56-v1 mAb CDRL3 (aa) 81 CSYAGSSTHV SARS-CoV-2 S2X56-v1 mAb VH (nt) 82 CAGGTCCAGCTGGTGCAATCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCT GGAGGCACCTTCGGCAGCTATACT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAAGG ATCATCCCTATCCTTAGTATACCA AACTACGCACAGAAGTTCCAGGGCAGAGTCACGTTTACCGCGGACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGT GCGAGAGGAGGGGGTGGGACCCACGCAGTTCCCCACTACTACTTTGACTCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X56-v1 mAb VL (nt) 83 CAGACTGTGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACC AGCAGTGATGTTGGGAGTTATAACCTT GTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTAT GAGGGCAGT AAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGC TGCTCATATGCAGGTAGTAGCACCCATGTC TTCGGAACTGGGACCAAGGTCATCGTCCTAG SARS-CoV-2 S2X58-v1 mAb VH (aa) 84 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTSYY MHWVRQAPGQGLEWMGI INRSGGST SYAQKFQGRVTMTRDTSTSTVYMDLSSLRSEDTAVYYCARDSGIAARVVYWGQGTLVTVSS SARS-CoV-2 S2X58-v1 mAb CDRH1 (aa) 85 GYTFTSYY SARS-CoV-2 S2X58-v1 mAb CDRH2 (aa) 86 INRSGGST SARS-CoV-2 S2X58-v1 mAb CDRH3 (aa) 87 ARDSGIAARVVY SARS-CoV-2 S2X58-v1 mAb VL (aa) 88 NIQMTQSPSSLSASVGDRVTITCQAS QDISNY LNWYQQKPGKVPKLLIY DAS NLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQHDNLFTFGPGTKVDIK SARS-CoV-2 S2X58-v1 mAb CDRL1 (aa) 89 QDISNY SARS-CoV-2 S2X58-v1 mAb CDRL2 (aa) 90 DAS SARS-CoV-2 S2X58-v1 mAb CDRL3 (aa) 91 QQHDNLFT SARS-CoV-2 S2X58-v1 mAb VH (nt) 92 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATCT GGATACACCTTCACCAGCTACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAATA ATCAACCGTAGTGGTGGTAGCACA AGCTACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGTCTACATGGACCTGAGCAGCCTGAGATCTGAGGACACGGCCGTCTATTACTGT GCGAGAGATTCGGGGATAGCAGCCAGGGTTGTCTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X58-v1 mAb VL (nt) 93 AACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGT CAGGACATTAGCAACTAT TTAAATTGGTATCAGCAGAAACCAGGGAAAGTCCCTAAGCTCCTGATCTAC GATGCATCC AATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGT CAACAGCATGATAATCTTTTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2X58-v2 mAb VL (aa) 94 DIVMTQSPSSLSASVGDRVTITCQAS QDISNY LNWYQQKPGKVPKLLIY DAS NLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQHDNLFTFGPGTKVDIK SARS-CoV-2 S2X58-v2 mAb VL (nt) 95 GACATCGTGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGT CAGGACATTAGCAACTAT TTAAATTGGTATCAGCAGAAACCAGGGAAAGTCCCTAAGCTCCTGATCTAC GATGCATCC AATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGT CAACAGCATGATAATCTTTTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2X71-v1 mAb VH (aa) 96 EVQLVESGGGLIQPGGSLRLSCAAS GFTVSANY MSWVRQTPGKGLEWVSV IYSGGST YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDLAAAAGP WGQGTLVTVSS SARS-CoV-2 S2X71-v1 mAb CDRH1 (aa) 97 GFTVSANY SARS-CoV-2 S2X71-v1 mAb CDRH2 (aa) 98 IYSGGST SARS-CoV-2 S2X71-v1 mAb CDRH3 (aa) 99 ARDLAAAAGP SARS-CoV-2 S2X71-v1 mAb VL (aa) 100 DIQMTQSPSSLSASVGDRVTITCRAS QGIRND LGWFQQKPGKAPKLLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYC LQDYNYPRT FGQGTKLEIK SARS-CoV-2 S2X71-v1 mAb CDRL1 (aa) 101 QGIRND SARS-CoV-2 S2X71-v1 mAb CDRL2 (aa) 102 AAS SARS-CoV-2 S2X71-v1 mAb CDRL3 (aa) 103 LQDYNYPRT SARS-CoV-2 S2X71-v1 mAb VH (nt) 104 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGGTTCACCGTCAGTGCCAACTAC ATGAGCTGGGTCCGCCAGACTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTT ATTTATAGCGGTGGTAGCACA TACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTACCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGT GCGAGAGATTTAGCTGCAGCTGCTGGGCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X71-v1 mAb VL (nt) 105 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGT CAGGGCATTAGAAATGAT TTAGGCTGGTTTCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT GCTGCATCC AGTTTACAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGCACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGT CTACAAGATTACAATTACCCTCGGACT TTTGGCCAGGGGACCAAGCTGGAGATCAAAC SARS-CoV-2 S2X76-v1 mAb VH (aa) 106 QVQLVQSGAEVKKPGASVKVSCKAS GYSFTNYY MHWVRQAPGQGLEWMGI INASGGST RYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGIAARVVYWGQGTLVTVSS SARS-CoV-2 S2X76-v1 mAb CDRH1 (aa) 107 GYSFTNYY SARS-CoV-2 S2X76-v1 mAb CDRH2 (aa) 108 INASGGST SARS-CoV-2 S2X76-v1 mAb CDRH3 (aa) 109 ARDSGIAARVVY SARS-CoV-2 S2X76-v1 mAb VL (aa) 110 AIRMTQSPSSLSASVGDRVTITCQAS QDISNY LNWYQQKPGKAPKLLIY DAS NLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQHDDLFTFGPGTKVDIK SARS-CoV-2 S2X76-v1 mAb CDRL1 (aa) 111 QDISNY SARS-CoV-2 S2X76-v1 mAb CDRL2 (aa) 112 DAS SARS-CoV-2 S2X76-v1 mAb CDRL3 (aa) 113 QQHDDLFT SARS-CoV-2 S2X76-v1 mAb VH (nt) 114 caggtccagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtttcctgcaaggcatct gggtacagcttcaccaactactat atgcactgggtgcgacaggcccctggacaagggcttgagtggatgggaata atcaacgctagtggtggtagcaca aggtacgcacagaagttccagggcagagtcaccatgaccagggacacgtccacgagcacagtctacatggagttgagcagcctgagatctgaggacacggccgtgtattactgt gcgagagattcggggatagcagccagggttgtctac tggggccagggaaccctggtcaccgtctcctcag SARS-CoV-2 S2X76-v1 mAb VL (nt) 115 GCCATCCGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGT CAGGACATTAGCAACTAT TTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAC GATGCATCC AATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCGACATATTACTGT CAACAACATGATGATCTTTTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2X76-v2 mAb VH (nt) 116 caggtccagcttgtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtttcctgcaaggcatct gggtacagcttcaccaactactat atgcactgggtgcgacaggcccctggacaagggcttgagtggatgggaata atcaacgctagtggtggtagcaca aggtacgcacagaagttccagggcagagtcaccatgaccagggacacgtccacgagcacagtctacatggagttgagcagcctgagatctgaggacacggccgtgtattactgt gcgagagattcggggatagcagccagggttgtctac tggggccagggaaccctggtcaccgtctcctcag SARS-CoV-2 S2X76-v3 mAb VH (nt) 117 caggtacagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtttcctgcaaggcatct gggtacagcttcaccaactactat atgcactgggtgcgacaggcccctggacaagggcttgagtggatgggaata atcaacgctagtggtggtagcaca aggtacgcacagaagttccagggcagagtcaccatgaccagggacacgtccacgagcacagtctacatggagttgagcagcctgagatctgaggacacggccgtgtattactgt gcgagagattcggggatagcagccagggttgtctac tggggccagggaaccctggtcaccgtctcctcag SARS-CoV-2 S2X76-v4 mAb VH (nt) 118 caggtacagcttgtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtttcctgcaaggcatct gggtacagcttcaccaactactat atgcactgggtgcgacaggcccctggacaagggcttgagtggatgggaata atcaacgctagtggtggtagcaca aggtacgcacagaagttccagggcagagtcaccatgaccagggacacgtccacgagcacagtctacatggagttgagcagcctgagatctgaggacacggccgtgtattactgt gcgagagattcggggatagcagccagggttgtctac tggggccagggaaccctggtcaccgtctcctcag SARS-CoV-2 S2X11-v1 mAb VH (aa) 119 EVQLVESGGGLVQPGSLRLSCAVS GFIVSSNY MTWVRQAPGKGLEWVSV IYSGGST FYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDFPVRRGVNIWGQGTLVTVSS SARS-CoV-2 S2X11-v1 mAb CDRH1 (aa) 120 GFIVSSNY SARS-CoV-2 S2X11-v1 mAb CDRH2 (aa) 121 IYSGGST SARS-CoV-2 S2X11-v1 mAb CDRH3 (aa) 122 ARDFPVRRGVNI SARS-CoV-2 S2X11-v1 mAb VL (aa) 123 DIQLTQSPSSLSASVGDRVTITCQAS QDIVNY LNWYQQKPGKAPKLLIY DAS NLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYC HQYDNLPPAFGGGTKVEIK SARS-CoV-2 S2X11-v1 mAb CDRL1 (aa) 124 QDIVNY SARS-CoV-2 S2X11-v1 mAb CDRL2 (aa) 125 DAS SARS-CoV-2 S2X11-v1 mAb CDRL3 (aa) 126 HQYDNLPPA SARS-CoV-2 S2X11-v1 mAb VH (nt) 127 GAGGTGCAACTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGTCTCT GGATTCATCGTCAGTAGCAACTAC ATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTT ATTTATAGCGGTGGTAGCACA TTCTACGCAGACTCCGTGAAGGGCCGATTCACCATTTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTATTGT GCGAGAGATTTCCCCGTACGTCGGGGAGTTAATATC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X11-v1 mAb VL (nt) 128 GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGT CAGGACATTGTCAACTAT TTAAATTGGTATCAACAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAC GATGCATCC AATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGT CACCAGTATGATAATCTCCCTCCGGCT TTCGGCGGAGGGACCAAGGTGGAGATCAAAC SARS-CoV-2 S2X35-v1 mAb VH (aa) 129 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTNYG ISWVRQAPGQGLEWMGW ISAYKGNT NYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARPDYQVLGYDFWIGYYGMDV WGQGTTVIVSS SARS-CoV-2 S2X35-v1 mAb CDRH1 (aa) 130 GYTFTNYG SARS-CoV-2 S2X35-v1 mAb CDRH2 (aa) 131 ISAYKGNT SARS-CoV-2 S2X35-v1 mAb CDRH3 (aa) 132 ARPDYQVLGYDFWIGYYGMDV SARS-CoV-2 S2X35-v1 mAb VL (aa) 133 QSVLTQPPSVSGAPGQRVTISCTGS SSNIGAGYD VHWYQQLPGTAPKLLIY GNT NRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYC QSYDSSLSGSEVVFGGGTKLTVL SARS-CoV-2 S2X35-v1 mAb CDRL1 (aa) 134 SSNIGAGYD SARS-CoV-2 S2X35-v1 mAb CDRL2 (aa) 135 GNT SARS-CoV-2 S2X35-v1 mAb CDRL3 (aa) 136 QSYDSSLSGSEVV SARS-CoV-2 S2X35-v1 mAb VH (nt) 137 CAGGTCCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGTTACACCTTTACCAACTATGGT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAGCGCTTACAAGGGTAACACA AACTATGCACAGAAACTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAGCACAGCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGACCCGATTATCAGGTCCTGGGGTACGATTTTTGGATTGGGTACTACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCATCGTCTCCTCA SARS-CoV-2 S2X35-v1 mAb VL (nt) 138 CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCAGGGCAGAGGGTCACCATCTCCTGCACTGGGAGC AGCTCCAACATCGGGGCAGGTTATGAT GTACACTGGTACCAGCAGCTTCCAGGAACAGCCCCCAAACTCCTCATCTAT GGTAACACC AATCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGATGAGGCTGATTATTACTGC CAGTCTTATGACAGCAGCCTGAGTGGTTCGGAGGTGGTG TTCGGCGGAGGGACCAAGCTGACCGTCCTAG SARS-CoV-2 S309 mAb VH (aa) 139 QVQLVQSGAEVKKPGASVKVSCKAS GYPFTSYG ISWVRQAPGQGLEWMGW ISTYNGNT NYAQKFQGRVTMTTDTSTTTGYMELRRLRSDDTAVYYC ARDYTRGAWFGESLIGGFDN WGQGTLVTVSS SARS-CoV-2 S309 mAb CDRH1 (aa) 140 GYPFTSYG SARS-CoV-2 S309 mAb CDRH2 (aa) 141 ISTYNGNT SARS-CoV-2 S309 mAb CDRH3 (aa) 142 ARDYTRGAWFGESLIGGFDN SARS-CoV-2 S309 mAb VL (aa) 143 EIVLTQSPGTLSLSPGERATLSCRAS QTVSSTS LAWYQQKPGQAPRLLIY GAS SRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQHDTSLTFGGGTKVEIK SARS-CoV-2 S309 mAb CDRL1 (aa) 144 QTVSSTS SARS-CoV-2 S309 mAb CDRL2 (aa) 145 GAS SARS-CoV-2 S309 mAb CDRL3 (aa) 146 QQHDTSLT SARS-CoV-2 S2X16-v2 mAb CDRH1 (aa) 147 GYIFTDHY MH SARS-CoV-2 S2X16-v2 mAb CDRH2 (aa) 148 WINPNSGGTNYAQKFQG SARS-CoV-2 S2X16-v2 mAb CDRH3 (aa) 149 DRSRFRFFSPDFDY SARS-CoV-2 S2X16-v3 mAb VH (aa) 150 EVQLVQSGAEVKKPGASVKVSCKAS GYIFTDHY MHWVRQAPGQGLEWMGF INPNSGGT NYAQKFQGRVTMTRDTSINTAYMELSRLRSDDTAVHYC ARDRSRFRFFSPDFDY WGQGTLVTVSS SARS-CoV-2 S2X16-v3 mAb CDRH2 (aa) 151 FINPNSGGTNYAQKFQG SARS-CoV-2 S2X16-v4 mAb CDRL1 (aa) 152 RSSQSLLHSNGYNYLD SARS-CoV-2 S2X16-v4 mAb CDRL2 (aa) 153 LGS NRAS SARS-CoV-2 S2X16-v5 mAb VL (aa) 154 EIVLTQSPLSLPVTPGEPASISCRSS QSLLHSQGYNY LDWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPPT FGQGTKVEIK SARS-CoV-2 S2X16-v5 mAb CDRL1 (aa) 155 RSSQSLLHSQGYNYLD SARS-CoV-2 S2X16-v6 mAb CDRL1 (aa) 156 QSLLHSQGYNY SARS-CoV-2 S2X16-v7 mAb VL (aa) 157 EIVLTQSPLSLPVTPGEPASISCRSS QSLLHSNAYNY LDWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPPT FGQGTKVEIK SARS-CoV-2 S2X16-v7 mAb CDRL1 (aa) 158 RSSQSLLHSNAYNYLD SARS-CoV-2 S2X16-v8 mAb CDRL1 (aa) 159 QSLLHSNAYNY SARS-CoV-2 S2X30-v2 mAb CDRH1 (aa) 160 GGTFGSYT IS SARS-CoV-2 S2X30-v2 mAb CDRH2 (aa) 161 RIIPILSIPNYAQKFQG SARS-CoV-2 S2X30-v2 mAb CDRH3 (aa) 162 GGGGTHAVPHYYFDS SARS-CoV-2 S2X30-v3 mAb VH (aa) 163 EVQLVQSGAEVKKPGSSVKVSCKAS GGTFGSYT ISWVRQAPGQGLEWMGR IIPILSIP NYAQKFQGRVTFTADKSTSTAYMELSSLRSEDTAVYYC ARGGGGTHAVPHYYFESWGQGTLVTVSS SARS-CoV-2 S2X30-v3 mAb CDRH3 (aa) 164 ARGGGGTHAVPHYYFES SARS-CoV-2 S2X30-v4 mAb CDRH3 (aa) 165 GGGGTHAVPHYYFES SARS-CoV-2 S2X30-v5 mAb CDRL1 (aa) 166 RASQSVSSNLA SARS-CoV-2 S2X30-v5 mAb CDRL2 (aa) 167 GAS TRAT SARS-CoV-2 S2X30-v6 mAb VH (aa) 168 EIVMMQSPATLSVSPGERATLSCRAS QSVSSN LAWYQHKPGQAPRLLIY GAS TRATGIPARFSGSGSGTEFTLTISSMQSEDFAVYYCQQYNNFPFTFGGGTKVEIK SARS-CoV-2 S2X30-v6 mAb CDRL3 (aa) 169 QQYNNFPFT SARS-CoV-2 S2X35-v2 mAb CDRH1 (aa) 170 GYTFTNYG IS SARS-CoV-2 S2X35-v2 mAb CDRH2 (aa) 171 WISAYKGNTNYAQKLQG SARS-CoV-2 S2X35-v2 mAb CDRH3 (aa) 172 PDYQVLGYDFWIGYYGMDV SARS-CoV-2 S2X35-v3 mAb VH (aa) 173 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTNYG ISWVRQAPGQGLEWMGF ISAYKGNT NYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARPDYQVLGYDFWIGYYGMDV WGQGTTVIVSS SARS-CoV-2 S2X35-v3 mAb CDRH1 (aa) 174 FISAYKGNTNYAQKLQG SARS-CoV-2 S2X35-v4 mAb VH (aa) 175 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTNYG ISWVRQAPGQGLEWMGW ISAYKGNT NYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARPDYQVLGYDFFIGYYGMDV WGQGTTVIVSS SARS-CoV-2 S2X35-v4 mAb CDRH3 (aa) 176 ARPDYQVLGYDFFIGYYGMDV SARS-CoV-2 S2X35-v5 mAb CDRH3 (aa) 177 PDYQVLGYDFFIGYYGMDV SARS-CoV-2 S2X35-v6 mAb VH (aa) 178 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTNYG ISWVRQAPGQGLEWMGF ISAYKGNT NYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYC ARPDYQVLGYDFFAGYYGMDV WGQGTTVIVSS SARS-CoV-2 S2X35-v6 mAb CDRH3 (aa) 179 ARPDYQVLGYDFFAGYYGMDV SARS-CoV-2 S2X35-v7 mAb CDRH3 (aa) 180 PDYQVLGYDFFAGYYGMDV SARS-CoV-2 S2X35-v8 mAb CDRL1 (aa) 181 TGSSSNIGAGYDVH SARS-CoV-2 S2X35-v8 mAb CDRL2 (aa) 182 GNT NRPS SARS-CoV-2 S2X47-v2 mAb CDRH1 (aa) 183 GGSISSRSYY WS SARS-CoV-2 S2X47-v2 mAb CDRH2 (aa) 184 RIYTSGNTNYNPSLRS SARS-CoV-2 S2X47-v2 mAb CDRH3 (aa) 185 ERIIGTAHVGGWFDP SARS-CoV-2 S2X47-v3 mAb VH (aa) 186 QVQLQESGPGLVKPSQTLSLTCTVS GGSISSRSYY WSWIRQPAGKGLEWIGR IYTSGNT NYNPSLRSRVTISVDTSKNQFSLKLGSVTAADTAVYYC ARERIIGTAHVGGFFDPWGQGTLVTVSS SARS-CoV-2 S2X47-v3 mAb CDRH3 (aa) 187 ARERIIGTAHVGGFFDP SARS-CoV-2 S2X47-v4 mAb CDRH3 (aa) 188 ERIIGTAHVGGFFDP SARS-CoV-2 S2X47-v5 mAb VH (aa) 189 QVQLQESGPGLVKPSQTLSLTCTVS GGSISSRSYY FSWIRQPAGKGLEWIGR IYTSGNT NYNPSLRSRVTISVDTSKNQFSLKLGSVTAADTAVYYC ARERIIGTAHVGGWFDPWGQGTLVTVSS SARS-CoV-2 S2X47-v5 mAb CDRH1 (aa) 190 GGSISSRSYY FS SARS-CoV-2 S2X47-v6 mAb VH (aa) 191 QVQLQESGPGLVKPSQTLSLTCTVS GGSISSRSYY FSWIRQPAGKGLEWIGR IYTSGNT NYNPSLRSRVTISVDTSKNQFSLKLGSVTAADTAVYYC ARERIIGTAHVGGFFDPWGQGTLVTVSS SARS-CoV-2 S2X47-v7 mAb CDRL1 (aa) 192 SGSSSNIGSDTVN SARS-CoV-2 S2X47-v7 mAb CDRL2 (aa) 193 TNN QRPS SARS-CoV-2 S2X47-v8 mAb VL (aa) 194 QTVVTQPPSASGTPGQRVTISCSGS SSNIGSDT VNWYLQLPGTAPKLLIY TNN QRPSGVPDRFSGSKSGTSASLAISGLQSEDEANYYC AAFDDSLNGFVFGGGTKLTVL SARS-CoV-2 S2X47-v8 mAb CDRL3 (aa) 195 AAFDDSLNGFV SARS-CoV-2 S2X47-v9 mAb VL (aa) 196 QTVVTQPPSASGTPGQRVTISCSGS SSNIGSDT VNWYLQLPGTAPKLLIY TNN QRPSGVPDRFSGSKSGTSASLAISGLQSEDEANYYC AAFDDSLNGWVFGGGTKLTVL SARS-CoV-2 S2X47-v9 mAb CDRL3 (aa) 197 AAFDDSLNGWV SARS-CoV-2 S2H30-v1 mAb VH (aa) 198 EVHLVESGGGLVQPGSLRLSCAAS GFIVSSNY MSWVRQAPGKGLEWVSV IYSGGST FYADSVKGRFTISRDNSKNTVYLQMNSLRVEDTAVYYC ARDMGGQPGGYFDY WGQGTLVTVSS SARS-CoV-2 S2H30-v1 mAb CDRH1 (aa) 199 GFIVSSNY SARS-CoV-2 S2H30-v1 mAb CDRH2 (aa) 200 IYSGGST SARS-CoV-2 S2H30-v1 mAb CDRH3 (aa) 201 ARDMGGQPGGYFDY SARS-CoV-2 S2H30-v1 mAb VL (aa) 202 DIVMTQSPSTLSASVGDRVTITCRAS QSFSSW LAWYQQKPGKAPKLLIY KAS NLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNTYATFGQGTKVEIK SARS-CoV-2 S2H30-v1 mAb CDRL1 (aa) 203 QSFSSW SARS-CoV-2 S2H30-v1 mAb CDRL2 (aa) 204 KAS SARS-CoV-2 S2H30-v1 mAb CDRL3 (aa) 205 QQYNTYAT SARS-CoV-2 S2H30-v1 mAb VH (nt) 206 GAGGTGCATCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCATCGTCAGTAGCAACTAC ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTT ATTTATAGCGGTGGTAGTACA TTCTACGCAGACTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGGTGTATCTTCAAATGAACAGCCTGAGAGTCGAGGACACGGCTGTGTATTACTGT GCGCGGGACATGGGGGGGCAGCCTGGAGGCTACTTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2H30-v1 mAb VL (nt) 207 GACATCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGT CAGAGTTTTAGTAGCTGG TTGGCCTGGTATCAGCAGAAACCAGGGAAGGCCCCTAAGCTCCTGATCTAT AAGGCATCT AATTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACTATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGC CAACAGTATAATACTTATGCGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAGC SARS-CoV-2 S2H37-v1 mAb VH (aa) 208 EVQLVESGGGLVQPGGSLRLSCAAS GLTVSSNY MSWVRQAPGKGLEWVSL IYSGGTT YYADSVKGRFTISRDNSKNTLYLQMNSLRTEDTAVYYC ARDPPHRSGGV WGQGTLVTVSS SARS-CoV-2 S2H37-v1 mAb CDRH1 (aa) 209 GLTVSSNY SARS-CoV-2 S2H37-v1 mAb CDRH2 (aa) 210 IYSGGTT SARS-CoV-2 S2H37-v1 mAb CDRH3 (aa) 211 ARDPPHRSGGV SARS-CoV-2 S2H37-v1 mAb VL (aa) 212 AIWMTQSPSSLSASVGDRVTITCQAS QDINNY LNWYQQKPGKAPKLLIY DAS NLETGVPSRFSGSGSGTYFTFTISSLQPEDIATYYC QQSDNLPITFGQGTRLEIK SARS-CoV-2 S2H37-v1 mAb CDRL1 (aa) 213 QDINNY SARS-CoV-2 S2H37-v1 mAb CDRL2 (aa) 214 DAS SARS-CoV-2 S2H37-v1 mAb CDRL3 (aa) 215 QQSDNLPIT SARS-CoV-2 S2H37-v1 mAb VH (nt) 216 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGTTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTGACCGTCAGTAGCAACTAC ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTT ATTTATAGCGGTGGTACCACA TACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACACTATATCTTCAAATGAACAGCCTGAGAACTGAGGACACGGCTGTGTATTACTGT GCGAGAGACCCTCCCCACCGCAGTGGCGGGGTC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2H37-v1 mAb VL (nt) 217 GCCATCTGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGT CAGGACATTAACAACTAT TTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTAC GATGCATCC AATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACATATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTACTGT CAACAGTCTGATAATCTCCCGATCACA TTCGGCCAAGGGACACGACTGGAGATTAAAC SARS-CoV-2 S2H40-v1 mAb VH (aa) 218 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY MHWVRQAPGQGLEWMGW INPISGAT NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYC ARVASSGWYELEILYGVDV WGQGTTVTVSS SARS-CoV-2 S2H40-v1 mAb CDRH1 (aa) 219 GYTFTGYY SARS-CoV-2 S2H40-v1 mAb CDRH2 (aa) 220 INPISGAT SARS-CoV-2 S2H40-v1 mAb CDRH3 (aa) 221 ARVASSGWYELEILYGVDV SARS-CoV-2 S2H40-v1 mAb VL (aa) 222 QSVLTQPASVSGSPGQSITISCTGT SSDVGGYNY VSWYQQHPGKAPKLMIY EVS NRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTQVFGTGTKVTVL SARS-CoV-2 S2H40-v1 mAb CDRL1 (aa) 223 SSDVGGYNY SARS-CoV-2 S2H40-v1 mAb CDRL2 (aa) 224 EVS SARS-CoV-2 S2H40-v1 mAb CDRL3 (aa) 225 SSYTSSSTQV SARS-CoV-2 S2H40-v1 mAb VH (nt) 226 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAGGGGCTTGAGTGGATGGGATGG ATCAACCCTATCAGTGGTGCCACA AACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGAGTAGCTAGCAGTGGCTGGTATGAACTGGAAATTCTCTACGGTGTGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2H40-v1 mAb VL (nt) 227 CAGTCTGTGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACC AGCAGTGACGTTGGTGGTTATAACTAT GTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTAT GAGGTCAGT AATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGC AGCTCATATACAAGCAGCAGCACTCAGGTC TTCGGAACTGGGACCAAGGTCACCGTCCTAG SARS-CoV-2 S2H58-v1 mAb VH (aa) 228 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGW INPNSGGT NFAQKFQGRVTMTRATSFSTAYMELSSLRSDDTAVYYC ASSGYLGYYYYGMDVWGQGTTVTVSS SARS-CoV-2 S2H58-v1 mAb CDRH1 (aa) 229 GYTFTGYY SARS-CoV-2 S2H58-v1 mAb CDRH2 (aa) 230 INPNSGGT SARS-CoV-2 S2H58-v1 mAb CDRH3 (aa) 231 ASSGYLGYYYYGMDV SARS-CoV-2 S2H58-v1 mAb VL (aa) 232 AIWMTQSPLSLPVTPGEPASISCRSS QSLLHSNVYNY LDWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPHT FGQGTKLEIK SARS-CoV-2 S2H58-v1 mAb CDRL1 (aa) 233 QSLLHSNVYNY SARS-CoV-2 S2H58-v1 mAb CDRL2 (aa) 234 LGS SARS-CoV-2 S2H58-v1 mAb CDRL3 (aa) 235 MQALQTPHT SARS-CoV-2 S2H58-v1 mAb VH (nt) 236 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTAT ATACACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTAACAGTGGTGGCACA AACTTTGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGCCACGTCCTTCAGCACAGCCTACATGGAGCTGAGCAGTCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGTAGTGGTTACCTCGGTTATTACTACTACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2H58-v1 mAb VL (nt) 237 GCCATCTGGATGACCCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGT CAGAGCCTCCTGCATAGTAATGTATACAACTAT TTGGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTAT TTGGGTTCT AATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGC ATGCAAGCTCTACAAACTCCTCACACT TTTGGCCAGGGGACCAAGCTGGAGATCAAAC SARS-CoV-2 S2H58-v2 mAb VL (aa) 238 DIVMTQTPLSLPVTPGEPASISCRSS QSLLHSNVYNY LDWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPHT FGQGTKLEIK SARS-CoV-2 S2H58-v2 mAb VL (nt) 239 GATATTGTGATGACCCAGACTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGT CAGAGCCTCCTGCATAGTAATGTATACAACTAT TTGGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTAT TTGGGTTCT AATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGC ATGCAAGCTCTACAAACTCCTCACACT TTTGGCCAGGGGACCAAGCTGGAGATCAAAC SARS-CoV-2 S2H62-v1 mAb VH (aa) 240 EVHLVESGGGLVQPGSLRLSCAAS VITVSSNY MSWVRQAPGKGLEWVSL IYSGGST YYADSVKGRFTISRDNFKNTLYLQMNSLRAEDTAVYYC ARDLDIAGGMDVWGQGTTVTVSS SARS-CoV-2 S2H62-v1 mAb CDRH1 (aa) 241 VITVSSNY SARS-CoV-2 S2H62-v1 mAb CDRH2 (aa) 242 IYSGGST SARS-CoV-2 S2H62-v1 mAb CDRH3 (aa) 243 ARDLDIAGGMDV SARS-CoV-2 S2H62-v1 mAb VL (aa) 244 DIVMTQTPSSLSASVGDRVTITCRAG QTISNY LNWYQQKPGKAPKLLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SARS-CoV-2 S2H62-v1 mAb CDRL1 (aa) 245 QTISNY SARS-CoV-2 S2H62-v1 mAb CDRL2 (aa) 246 AAS SARS-CoV-2 S2H62-v1 mAb CDRL3 (aa) 247 QQSYSTPYT SARS-CoV-2 S2H62-v1 mAb VH (nt) 248 GAGGTGCATCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GTAATCACCGTCAGTAGCAACTAC ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTT ATTTATAGCGGTGGTAGCACA TACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTTCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGT GCGAGAGATCTGGATATAGCAGGCGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2H62-v1 mAb VL (nt) 249 gatattgtgatgacccagactccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaggt cagaccattagcaactat ttaaattggtatcagcagaaaccagggaaagcccctaagctcctgatctat gctgcatcc agtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcaacttactactgt caacagagttacagtaccccgtacact tttggccaggggaccaagctggagatcaaac SARS-CoV-2 S2H62-v2 mAb VL (aa) 250 DIGMTQTPSSLSASVGDRVTITCRAG QTISNY LNWYQQKPGKAPKLLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SARS-CoV-2 S2H62-v2 mAb VL (nt) 251 gatattgggatgacccagactccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaggtcagaccattagcaactatttaaattggtatcagcagaaaccagggaaagcccctaagctcctgatctatgctgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcaacttactactgtcaacagagttacagtaccccgtacacttttggccaggggaccaagctggagatcaaac SARS-CoV-2 S2H62-v3 mAb VL (aa) 252 DIQLTQSPSSLSASVGDRVTITCRAG QTISNY LNWYQQKPGKAPKLLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK SARS-CoV-2 S2H62-v3 mAb VL (nt) 253 gacatccagttgacccagtctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaggt cagaccattagcaactat ttaaattggtatcagcagaaaccagggaaagcccctaagctcctgatctat gctgcatcc agtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcaacttactactgt caacagagttacagtaccccgtacact tttggccaggggaccaagctggagatcaaa SARS-CoV-2 S2H66-v1 mAb VH (aa) 254 EVQLQESGPGLVKPSETLSLTCSVS GGSISSYY WSWIRQPPGKALEWIGY IYYSGST NYNSSLKSRVTISLDTSKNQFSLKLSSVAAADTAVYYC ARHDPFRAVTGHFDYWGQGTLVTVSS SARS-CoV-2 S2H66-v1 mAb CDRH1 (aa) 255 GGSISSYY SARS-CoV-2 S2H66-v1 mAb CDRH2 (aa) 256 IYYSGST SARS-CoV-2 S2H66-v1 mAb CDRH3 (aa) 257 ARHDPFRAVTGHFDY SARS-CoV-2 S2H66-v1 mAb VL (aa) 258 QTVLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTIVIYEDS RRPSGVPDRFSGSIDSSSSNSASLSISRLKTEDEADYYCQSYYRNTVVFGGGTKLTVL _ SARS-CoV-2 S2H66-v1 mAb CDRL1 (aa) 259 SGSIASNY SARS-CoV-2 S2H66-v1 mAb CDRL2 (aa) 260 EDS SARS-CoV-2 S2H66-v1 mAb CDRL3 (aa) 261 QSYYRNTVV SARS-CoV-2 S2H66-v1 mAb VH (nt) 262 GAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCTCTGTCTCT GGTGGCTCCATCAGTAGTTACTAC TGGAGCTGGATCCGGCAGCCCCCAGGGAAGGCACTGGAGTGGATTGGATAT ATCTATTACAGTGGGAGCACC AACTACAATTCATCCCTCAAGAGTCGAGTCACCATATCACTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGGCCGCCGCAGACACGGCCGTGTATTACTGT GCGAGACATGACCCTTTCAGGGCAGTGACTGGGCACTTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2H66-v1 mAb VL (nt) 263 cagactgtgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagc agtggcagcattgccagcaactat gtgcagtggtaccaacagcgcccgggcagttcccccaccattgtgatctat gaggatagc cgaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcagcatctctagactgaagactgaggacgaggctgactactactgt cagtcttattatagaaacactgtggta ttcggcggagggaccaagctgaccgtcctag SARS-CoV-2 S2H70-v1 mAb VH (aa) 264 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY LHWVRQAPGQGLEWMGW INPISGGT NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYC ARVDYDILTGYYWGWFDP WGQGTLVTVSS SARS-CoV-2 S2H70-v1 mAb CDRH1 (aa) 265 GYTFTGYY SARS-CoV-2 S2H70-v1 mAb CDRH2 (aa) 266 INPISGGT SARS-CoV-2 S2H70-v1 mAb CDRH3 (aa) 267 ARVDYDILTGYYWGWFDP SARS-CoV-2 S2H70-v1 mAb VL (aa) 268 QTVVTQPASVSGSPGQSITISCTGT SSDVGGYNY VSWYQQHPGKAPKLMIY DVS NRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSTYVFGTGTKVTVL SARS-CoV-2 S2H70-v1 mAb CDRL1 (aa) 269 SSDVGGYNY SARS-CoV-2 S2H70-v1 mAb CDRL2 (aa) 270 DVS SARS-CoV-2 S2H70-v1 mAb CDRL3 (aa) 271 SSYTSSSTYV SARS-CoV-2 S2H70-v1 mAb VH (nt) 272 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTAT CTGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTATCAGTGGTGGCACA AACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGAGTGGATTACGATATTTTGACTGGTTATTACTGGGGCTGGTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2H70-v1 mAb VL (nt) 273 CAGACTGTGGTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACC AGCAGTGACGTTGGTGGTTATAACTAT GTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTAT GATGTCAGT AATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGC AGCTCATATACAAGCAGCAGCACTTATGTC TTCGGAACTGGGACCAAGGTCACCGTCCTAG SARS-CoV-2 S2H71-v1 mAb VH (aa) 274 QITLKESGPTLVKPTQTLTLTCTFS GFSLSTGGVG VGWIRQPPGKALEWLAL IYWDDDK RYSPSLKSRLTITKDTSKNQVVLTMTNVDPVDTATYYC ARHTVTRIFDYWGQGTLVTVSS SARS-CoV-2 S2H71-v1 mAb CDRH1 (aa) 275 GFSLSTGGVG SARS-CoV-2 S2H71-v1 mAb CDRH2 (aa) 276 IYWDDDK SARS-CoV-2 S2H71-v1 mAb CDRH3 (aa) 277 ARHTVTRIFDY SARS-CoV-2 S2H71-v1 mAb VL (aa) 278 QSVLTQPASVSGSPGQSITISCTGT SSDVGGFLY VSWYQQLPGKAPKLMIY EVS DRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTTSSTVFGGGTKLTVL SARS-CoV-2 S2H71-v1 mAb CDRL1 (aa) 279 SSDVGGFLY SARS-CoV-2 S2H71-v1 mAb CDRL2 (aa) 280 EVS SARS-CoV-2 S2H71-v1 mAb CDRL3 (aa) 281 SSYTTSSTV SARS-CoV-2 S2H71-v1 mAb VH (nt) 282 CAGATCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAAACCCACACAGACCCTCACGCTGACCTGCACCTTCTCT GGGTTCTCACTCAGCACTGGTGGAGTGGGT GTGGGCTGGATCCGTCAGCCCCCAGGAAAGGCCCTGGAGTGGCTTGCACTC ATTTATTGGGATGATGATAAG CGCTACAGCCCATCTCTGAAGAGCAGGCTCACCATCACCAAGGACACTTCCAAAAACCAGGTGGTCCTTACAATGACCAACGTGGACCCTGTGGACACAGCCACATATTACTGT GCACGCCATACGGTGACTAGGATATTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2H71-v1 mAb VL (nt) 283 CAGTCTGTGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACC AGCAGTGACGTTGGTGGTTTTCTCTAT GTCTCCTGGTACCAACAACTCCCAGGCAAAGCCCCCAAACTCATGATTTAT GAGGTCAGT GATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGC AGCTCATATACAACCAGCAGCACGGTG TTCGGCGGAGGGACCAAGTTGACCGTCCTAG SARS-CoV-2 S2H73-v1 mAb VH (aa) 284 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGW INPNSGGT NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYC ARELLVPGAMSPYGMDV WGQGTTVTVSS SARS-CoV-2 S2H73-v1 mAb CDRH1 (aa) 285 GYTFTGYY SARS-CoV-2 S2H73-v1 mAb CDRH2 (aa) 286 INPNSGGT SARS-CoV-2 S2H73-v1 mAb CDRH3 (aa) 287 ARELLVPGAMSPYGMDV SARS-CoV-2 S2H73-v1 mAb VL (aa) 288 EIVMTQSPATLSLSPGERATLSCRAS QSVSRY LAWYQQKPGQAPRLLIY DAS NRAAGIPARFSGSGSGTDFTLTISSLEPEDFVVYYC QQRSNWPPLAFGGGTKVEIK SARS-CoV-2 S2H73-v1 mAb CDRL1 (aa) 289 QSVSRY SARS-CoV-2 S2H73-v1 mAb CDRL2 (aa) 290 DAS SARS-CoV-2 S2H73-v1 mAb CDRL3 (aa) 291 QQRSNWPPLA SARS-CoV-2 S2H73-v1 mAb VH (nt) 292 CAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTAT ATACACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTAACAGTGGTGGCACA AACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGGGAATTATTAGTACCAGGTGCTATGTCCCCTTACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2H73-v1 mAb VL (nt) 293 GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGT CAGAGTGTTAGCAGGTAC TTAGCCTGGTACCAACAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTAT GATGCATCC AACAGGGCCGCTGGCATCCCAGCCAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGATTTTGTAGTTTATTACTGT CAGCAGCGTAGCAACTGGCCTCCGCTCGCT TTCGGCGGAGGGACCAAGGTGGAGATCAAAC SARS-CoV-2 S2H66-v2 mAb VL (aa) 294 SYELTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTIVIYEDS RRPSGVPDRFSGSIDSSSSNSASLSISRLKTEDEADYYCQSYYRNTVVFGGGTKLTVL _ SARS-CoV-2 S2H66-v2 mAb VL (nt) 295 tcctatgagctgacacagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccaacagcgcccgggcagttcccccaccattgtgatctatgaggatagccgaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcagcatctctagactgaagactgaggacgaggctgactactactgtcagtcttattatagaaacactgtggtattcggcggagggaccaagctgaccgtccta SARS-CoV-2 S2H66-v3 mAb VL (aa) 296 QPVLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTIVIYEDS RRPSGVPDRFSGSIDSSSSNSASLSISRLKTEDEADYYCQSYYRNTVVFGGGTKLTVL _ SARS-CoV-2 S2H66-v3 mAb VL (nt) 297 Cagcctgtgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccaacagcgcccgggcagttcccccaccattgtgatctatgaggatagccgaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcagcatctctagactgaagactgaggacgaggctgactactactgtcagtcttattatagaaacactgtggtattcggcggagggaccaagctgaccgtccta SARS-CoV-2 S2N12-v1 mAb VH (aa) 298 QVRLQESGPGLVKPSETLSLTCTVS GGSISSSTYF WGWIRQPPGKGLEWIGS ISYSGST YYNPSLKSRVTISVDTSKSQFSLKLSSVTAADTAVYYC ARRGGYCSRVNCYNRYWYFDL WGRGTLVTVSS SARS-CoV-2 S2N12-v1 mAb CDRH1 (aa) 299 GGSISSSTYF SARS-CoV-2 S2N12-v1 mAb CDRH2 (aa) 300 ISYSGST SARS-CoV-2 S2N12-v1 mAb CDRH3 (aa) 301 ARRGGYCSRVNCYNRYWYFDL SARS-CoV-2 S2N12-v1 mAb VL (aa) 302 DIQLTQSPSSVSASVGDRVTVSCRAS QDISSW LAWYQQKPGKAPKLLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYFCQQANSFPVTFGPGTKVDIK SARS-CoV-2 S2N12-v1 mAb CDRL1 (aa) 303 QDISSW SARS-CoV-2 S2N12-v1 mAb CDRL2 (aa) 304 AAS SARS-CoV-2 S2N12-v1 mAb CDRL3 (aa) 305 QQANSFPVT SARS-CoV-2 S2N12-v1 mAb VH (nt) 306 CAGGTGCGGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCT GGTGGCTCCATCAGCAGTAGTACTTACTTC TGGGGCTGGATCCGCCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGAGT ATCTCTTATAGTGGGAGCACC TACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCCGTTGACACGTCCAAGAGCCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCAGACACGGCTGTGTATTACTGT GCGAGACGGGGGGGATATTGTAGTCGTGTTAACTGCTACAATCGCTACTGGTACTTCGATCTC TGGGGCCGTGGCACCCTGGTCACTGTCTCCTCAG SARS-CoV-2 S2N12-v1 mAb VL (nt) 307 GACATCCAGTTGACGCAGTCTCCATCTTCTGTGTCTGCATCTGTAGGAGACAGAGTCACCGTCAGTTGTCGGGCGAGT CAGGATATTAGCAGCTGG TTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT GCTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACTATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTTTTGTCAACAGGCTAACAGTTTCCCTGTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2N12-v2 mAb VL (aa) 308 DIVMTQSPSSVSASVGDRVTVSCRAS QDISSW LAWYQQKPGKAPKLLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYFCQQANSFPVTFGPGTKVDIK SARS-CoV-2 S2N12-v2 mAb VL (nt) 309 GACATCGTGATGACCCAGTCTCCATCTTCTGTGTCTGCATCTGTAGGAGACAGAGTCACCGTCAGTTGTCGGGCGAGT CAGGATATTAGCAGCTGG TTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT GCTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACTATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTTTTGT CAACAGGCTAACAGTTTCCCTGTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2N12-v3 mAb VL (aa) 310 NIQMTQSPSSVSASVGDRVTVSCRAS QDISSW LAWYQQKPGKAPKLLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYFCQQANSFPVTFGPGTKVDIK SARS-CoV-2 S2N12-v3 mAb VL (nt) 311 AACATCCAGATGACCCAGTCTCCATCTTCTGTGTCTGCATCTGTAGGAGACAGAGTCACCGTCAGTTGTCGGGCGAGT CAGGATATTAGCAGCTGG TTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT GCTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACTATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTTTTGT CAACAGGCTAACAGTTTCCCTGTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2N22-v1 mAb VH (aa) 312 EVQLVESGGGLVQPGSLRLSCAAS GFTFSSYP MSWVRQAPGKGLEWVSA ISGSGNYT YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDPGGLSNFDFWGQGTLVTVSS SARS-CoV-2 S2N22-v1 mAb CDRH1 (aa) 313 GFTFSSYP SARS-CoV-2 S2N22-v1 mAb CDRH2 (aa) 314 ISGSGNYT SARS-CoV-2 S2N22-v1 mAb CDRH3 (aa) 315 AKDPGGLSNFDF SARS-CoV-2 S2N22-v1 mAb VL (aa) 316 NIQMTQSPSSLSASVGDRVTITCRAS QSISTY LNWFQQKPGKAPKLLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQREDFATYYCQQTYSTPRIFGQGTKLEIK SARS-CoV-2 S2N22-v1 mAb CDRL1 (aa) 317 QSISTY SARS-CoV-2 S2N22-v1 mAb CDRL2 (aa) 318 AAS SARS-CoV-2 S2N22-v1 mAb CDRL3 (aa) 319 QQTYSTPRI SARS-CoV-2 S2N22-v1 mAb VH (nt) 320 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCACCTTTAGCAGTTATCCT ATGAGCTGGGTCCGCCAGGCTCCAGGTAAGGGGCTGGAGTGGGTCTCAGCT ATTAGTGGTAGTGGTAATTACACA TACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGTTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGT GCGAAAGATCCCGGTGGGTTGTCGAACTTTGACTTC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2N22-v1 mAb VL (nt) 321 AACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGT CAGAGCATTAGCACCTAT TTAAATTGGTTTCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT GCTGCATCC AGTTTGCAAAGTGGGGTCCCGTCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTACAACGTGAAGATTTTGCAACTTACTACTGT CAACAGACTTACAGTACCCCTCGAATT TTTGGCCAGGGGACCAAGCTGGAGATCAAAC SARS-CoV-2 S2N25-v1 mAb VH (aa) 322 QVQLQESGPGLVKPSETLSLTCTVS GGSISSSY WSWIRQPPGKGLEWIGY LYYSGST NYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYC ARDPGPYYYDSSGYYLDAFD IWGQGTMVTVSS SARS-CoV-2 S2N25-v1 mAb CDRH1 (aa) 323 GGSISSSY SARS-CoV-2 S2N25-v1 mAb CDRH2 (aa) 324 LYYSGST SARS-CoV-2 S2N25-v1 mAb CDRH3 (aa) 325 ARDPGPYYYDSSGYYLDAFD SARS-CoV-2 S2N25-v1 mAb VL (aa) 326 AIWMTQSPSSLSASVGDRVTITCRASQSIVSY LNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYNTLSLTFGGGTKVEIK _ SARS-CoV-2 S2N25-v1 mAb CDRL1 (aa) 327 QSIVSY SARS-CoV-2 S2N25-v1 mAb CDRL2 (aa) 328 AAS SARS-CoV-2 S2N25-v1 mAb CDRL3 (aa) 329 QQTYNTLSLT SARS-CoV-2 S2N25-v1 mAb VH (nt) 330 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCT GGTGGCTCCATCAGTAGTTCCTAC TGGAGCTGGATCCGGCAGCCCCCAGGGAAGGGACTGGAGTGGATTGGCTAT CTCTATTACAGTGGGAGCACC AACTACAACCCCTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGACCTCTGTGACCGCTGCGGACACGGCCGTGTATTACTGT GCGAGAGACCCCGGGCCGTATTACTATGATAGTAGTGGTTATTACCTGGATGCTTTTGAT ATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAG SARS-CoV-2 S2N25-v1 mAb VL (nt) 331 GCCATCTGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGT CAGAGCATTGTCAGCTAT TTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT GCTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGT CAACAGACTTACAATACCCTTTCGCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAAC SARS-CoV-2 S2N28-v1 mAb VH (aa) 332 EVQLVESGGGVVQPGRSLRLSCAAS GFTFFSYG MHWVRQAPGKGLEWVAF IRYDGSNK YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDSPRVTSGGYYSYYYGMDV WGQGTTVTVSS SARS-CoV-2 S2N28-v1 mAb CDRH1 (aa) 333 GFTFFSYG SARS-CoV-2 S2N28-v1 mAb CDRH2 (aa) 334 IRYDGSNK SARS-CoV-2 S2N28-v1 mAb CDRH3 (aa) 335 AKDSPRVTSGGYYSYYYGMDV SARS-CoV-2 S2N28-v1 mAb VL (aa) 336 DIVMTQTPSSLSASVGDRVTITCRAS QNISSY LNWYQQKPRKAPKLLIY PAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK SARS-CoV-2 S2N28-v1 mAb CDRL1 (aa) 337 QNISSY SARS-CoV-2 S2N28-v1 mAb CDRL2 (aa) 338 PAS SARS-CoV-2 S2N28-v1 mAb CDRL3 (aa) 339 QQSYSTPLT SARS-CoV-2 S2N28-v1 mAb VH (nt) 340 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCT GGATTCACCTTCTTTAGCTATGGA ATGCACTGGGTCCGCCAGGCCCCGGGCAAGGGGCTGGAGTGGGTGGCATTT ATACGGTATGATGGAAGTAATAAA TACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACAGCTGTGTATTACTGT GCGAAAGACTCTCCTCGGGTTACCAGTGGCGGATATTACTCCTACTACTACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2N28-v1 mAb VL (nt) 341 GATATTGTGATGACCCAGACTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGT CAGAACATTAGCAGTTAT TTAAATTGGTATCAGCAGAAACCACGGAAAGCCCCTAAACTCCTGATCTAT CCTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGT CAACAGAGTTACAGTACGCCGCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAAC SARS-CoV-2 S309-v2 mAb VH (aa) 342 QVQLVQSGAEVKKPGASVKVSCKAS GYPFTSYG ISWVRQAPGQGLEWMGW ISTYQGNT NYAQKFQGRVTMTTDTSTTTGYMELRRLRSDDTAVYYC ARDYTRGAWFGESLIGGFDN WGQGTLVTVSS SARS-CoV-2 S309-v2 mAb CDRH1 (aa) 343 GYPFTSYG SARS-CoV-2 S309-v2 mAb CDRH2 (aa) 344 ISTYQGNT SARS-CoV-2 S309-v2 mAb CDRH3 (aa) 345 ARDYTRGAWFGESLIGGFDN SARS-CoV-2 S309-v2 mAb VL (aa) 346 EIVLTQSPGTLSLSPGERATLSCRASQTVSSTSLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQHDTSLTFGGGTKVEIK SARS-CoV-2 S309-v2 mAb CDRL1 (aa) 347 QTVSSTS SARS-CoV-2 S309-v2 mAb CDRL2 (aa) 348 GAS SARS-CoV-2 S309-v2 mAb CDRL3 (aa) 349 QQHDTSLT SARS-CoV-2 S2H58-v3 mAb VH (aa) 350 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGF INPNSGGT NFAQKFQGRVTMTRATSFSTAYMELSSLRSDDTAVYYC ASSGYLGYYYYGMDVWGQGTTVTVSS SARS-CoV-2 S2H58-v4 mAb VH (aa) 351 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGF INPNAGGT NFAQKFQGRVTMTRATSFSTAYMELSSLRSDDTAVYYC ASSGYLGYYYYGMDVWGQGTTVTVSS SARS-CoV-2 S2H58-v4 mAb CDRH2 (aa) 352 INPNAGGT SARS-CoV-2 S2H58-v5 mAb VH (aa) 353 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGF INPASGGT NFAQKFQGRVTMTRATSFSTAYMELSSLRSDDTAVYYC ASSGYAGYYYYGMDVWGQGTTVTVSS SARS-CoV-2 S2H58-v5 mAb CDRH3 (aa) 354 ASSGYAGYYYYGMDV SARS-CoV-2 S2H58-v6 mAb VL (aa) 355 DIVMTQTPLSLPVTPGEPASISCRSS QSLLHSNGYNY LDWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTPHTFGQGTKLEIK SARS-CoV-2 S2H58-v6 mAb CDRL1 (aa) 356 QSLLHSNGYNY SARS-CoV-2 S2H58-v7 mAb VL (aa) 357 DIVMTQTPLSLPVTPGEPASISCRSS QSLLHSNVYNY LDWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC IQALQTPHT FGQGTKLEIK SARS-CoV-2 S2H58-v7 mAb CDRL3 (aa) 358 IQALQTPHT SARS-CoV-2 S2N22-v2 mAb VH (aa) 359 EVQLVESGGGLVQPGSLRLSCAAS GFTFSSYP MSWVRQAPGKGLEWVSA ISGSGQYT YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDPGGLSNFDFWGQGTLVTVSS SARS-CoV-2 S2N22-v2 mAb CDRH2 (aa) 360 ISGSGQYT SARS-CoV-2 S2N22-v3 mAb VH (aa) 361 EVQLVESGGGLVQPGSLRLSCAAS GFTFSSYP MSWVRQAPGKGLEWVSA ISGSGGYT YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDPGGLSNFDFWGQGTLVTVSS SARS-CoV-2 S2N22-v3 mAb CDRH2 (aa) 362 ISGSGGYT SARS-CoV-2 S2N22-v4 mAb VH (aa) 363 EVQLVESGGGLVQPGSLRLSCAAS GFTFSSYP MSWVRQAPGKGLEWVSA ISGSGNYA YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDPGGLSNFDFWGQGTLVTVSS SARS-CoV-2 S2N22-v4 mAb CDRH2 (aa) 364 ISGSGNYA SARS-CoV-2 S2N22-v5 mAb VH (aa) 365 EVQLVESGGGLVQPGSLRLSCAAS GFTFSSYP MSWVRQAPGKGLEWVSA ISGSGNPT YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDPGGLSNFDFWGQGTLVTVSS SARS-CoV-2 S2N22-v5 mAb CDRH2 (aa) 366 ISGSGNPT SARS-CoV-2 S2N22-v6 mAb VH (aa) 367 EVQLVESGGGLVQPGSLRLSCAAS GFTFSSYP MSWVRQAPGKGLEWVSA ISGSGNYA YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDPGGLSNFDFWGQGTLVTVSS SARS-CoV-2 S2N22-v7 mAb VH (aa) 368 EVQLVESGGGLVQPGSLRLSCAAS GFTFSSYP ISWVRQAPGKGLEWVSA ISGSGNYA YYADAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDPGGLSNFDFWGQGTLVTVSS SARS-CoV-2 S2E6-v1 mAb VH (aa) 369 QITLKESGPTLVKPTQTLTLTCTFS GFSLSTSGVG VGWIRQPPGEALEWLAL IFWDDDK RYRPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYC AHRRTSYGSYYFDYWGQGTLVTVSS SARS-CoV-2 S2E6-v1 mAb CDRH1 (aa) 370 GFSLSTSGVG SARS-CoV-2 S2E6-v1 mAb CDRH2 (aa) 371 IFWDDDK SARS-CoV-2 S2E6-v1 mAb CDRH3 (aa) 372 AHRRTSYGSYYFDY SARS-CoV-2 S2E6-v1 mAb VL (aa) 373 DIEMTQSPSTLSASVGDRVTITCRAS QSISNW LAWYQQKPGRAPKLLIY RAS NLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPTFGQGTKVEIK SARS-CoV-2 S2E6-v1 mAb CDRL1 (aa) 374 QSISNW SARS-CoV-2 S2E6-v1 mAb CDRL2 (aa) 375 RAS SARS-CoV-2 S2E6-v1 mAb CDRL3 (aa) 376 QQYNSYPT SARS-CoV-2 S2E6-v1 mAb VH (nt) 377 CAGATCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAAACCCACACAGACCCTCACGCTGACCTGCACCTTCTCT GGGTTCTCACTCAGCACTAGTGGAGTGGGT GTGGGCTGGATCCGTCAGCCCCCAGGAGAGGCCCTGGAGTGGCTTGCACTC ATTTTTTGGGATGATGATAAG CGCTACAGGCCATCTCTGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCCTGTGGACACAGCCACATATTACTGT GCACACAGACGTACCAGCTATGGTTCTTACTACTTTGACTAT TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2E6-v1 mAb VL (nt) 378 GACATCGAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGT CAGAGTATTAGTAACTGG TTGGCCTGGTATCAGCAGAAACCAGGGAGAGCCCCTAAGCTCCTAATCTAT AGGGCGTCT AATTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGC CAACAGTATAATAGTTATCCGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAAC SARS-CoV-2 S2E7-v1 mAb VH (aa) 379 EVQLVESGGGLVQPGSLRLSCAAS GLTVSSNY MTWVRQAPGKGLEWVSI IYSGGST FYADSVKGRFTISRDNSKNTLNLQMNSLRVEDTAVYYC ARPIVGSRAGMDVWGQGTTVTVSS SARS-CoV-2 S2E7-v1 mAb CDRH1 (aa) 380 GLTVSSNY SARS-CoV-2 S2E7-v1 mAb CDRH2 (aa) 381 IYSGGST SARS-CoV-2 S2E7-v1 mAb CDRH3 (aa) 382 ARPIVGSRAGMDV SARS-CoV-2 S2E7-v1 mAb VH (aa) 383 EIVMTQSPSSLSASVGDRVTITCQAS QDINKY LNWYQQKPGKAPKLLIY DAS NLETGVPSRFSGSGSGTDFAFTISSLQPEDVATYYC HQYDNLPLTFGGGTKVEIK SARS-CoV-2 S2E7-v1 mAb CDRL1 (aa) 384 QDINKY SARS-CoV-2 S2E7-v1 mAb CDRL2 (aa) 385 DAS SARS-CoV-2 S2E7-v1 mAb CDRL3 (aa) 386 HQYDNLPLT SARS-CoV-2 S2E7-v1 mAb VH (nt) 387 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTAACTGTCAGTAGCAACTAC ATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAATT ATTTATAGCGGTGGTAGCACA TTCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGAATCTTCAAATGAACAGCCTGAGAGTTGAGGACACGGCTGTGTATTACTGT GCGAGACCCATAGTGGGATCCAGAGCCGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2E7-v1 mAb VL (nt) 388 GAAATAGTGATGACGCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGT CAAGACATTAACAAGTAT TTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTTATCTAC GATGCATCC AATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGGTCTGGGACAGATTTTGCTTTCACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACATATTACTGT CACCAGTATGATAATCTCCCGCTCACT TTCGGCGGAGGGACCAAGGTGGAGATCAAAC SARS-CoV-2 S2E9-v1 mAb VH (aa) 389 EVQLVESGGGLIQPGGSLRLSCAAS GLTVSSNY MSWVRQAPGKGLEWVSV IYSGGST FYAESVKGRFTISRDNSKNTLYLQLNSLRAADTAVYYC ARDLEIHGMDV WGQGTTVTVSS SARS-CoV-2 S2E9-v1 mAb CDRH1 (aa) 390 GLTVSSNY SARS-CoV-2 S2E9-v1 mAb CDRH2 (aa) 391 IYSGGST SARS-CoV-2 S2E9-v1 mAb CDRH3 (aa) 392 ARDLEIHGMDV SARS-CoV-2 S2E9-v1 mAb VL (aa) 393 EIVLTQSPSFLSASVGDRVTITCRAS QGISNY LAWYQQKPGKAPQLLIY AAS TLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPPVTFGPGTKVDIK SARS-CoV-2 S2E9-v1 mAb CDRL1 (aa) 394 QGISNY SARS-CoV-2 S2E9-v1 mAb CDRL2 (aa) 395 AAS SARS-CoV-2 S2E9-v1 mAb CDRL3 (aa) 396 QQLNSYPPVT SARS-CoV-2 S2E9-v1 mAb VH (nt) 397 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGGTTAACCGTCAGTAGCAACTAC ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTT ATTTATAGCGGTGGTAGCACA TTCTACGCAGAATCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAATTGAACAGCCTGAGAGCCGCGGACACGGCCGTGTATTACTGT GCGAGAGATCTTGAGATTCACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2E9-v1 mAb VL (nt) 398 GAAATTGTGCTGACTCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGT CAGGGCATTAGCAATTAT TTAGCCTGGTATCAGCAAAAACCAGGGAAAGCCCCTCAGCTCCTGATCTAT GCTGCATCC ACTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGT CAACAGCTTAATAGTTACCCTCCGGTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2E12-v1 mAb VH (aa) 399 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGW IVVGSGNT NYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCAS PYCSGGSCSDGFDIWGQGTMVTVSS SARS-CoV-2 S2E12-v1 mAb CDRH1 (aa) 400 GFTFTSSA SARS-CoV-2 S2E12-v1 mAb CDRH2 (aa) 401 IVVGSGNT SARS-CoV-2 S2E12-v1 mAb CDRH3 and N-terminal Ala-Ser (aa) 402 ASPYCSGGSCSDGFDI SARS-CoV-2 S2E12-v1 mAb VL (aa) 403 DIVLTQTPGTLSLSPGERATLSCRAS QSVSSSY LAWYQQKPGQAPRLLIY GAS SRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYVGLTGWTFGQGTKVEIK SARS-CoV-2 S2E12-v1 mAb CDRL1 (aa) 404 QSVSSSY SARS-CoV-2 S2E12-v1 mAb CDRL2 (aa) 405 GAS SARS-CoV-2 S2E12-v1 mAb CDRL3 (aa) 406 QQYVGLTGWT SARS-CoV-2 S2E12-v1 mAb VH (nt) 407 CAGGTGCAGCTGGTGCAGTCTGGGCCTGAGGTGAAGAAGCCTGGGACCTCAGTGAGGGTCTCCTGCAAGGCTTCT GGATTCACCTTTACTAGCTCTGCT GTACAGTGGGTGCGACAGGCTCGTGGACAACGCCTTGAGTGGGTGGGATGG ATCGTCGTTGGCAGTGGTAACACA AACTACGCACAGAAGTTCCACGAAAGAGTCACCATTACCAGGGACATGTCCACAAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCCGAGGACACGGCCGTGTATTACTGTGCGTCA CCTTATTGTAGTGGTGGTAGCTGCTCTGATGGTTTTGATATC TGGGGCCAAGGGACAATGGTCACCGTCTCTTCAG SARS-CoV-2 S2E12-v1 mAb VL (nt) 408 GATATTGTGTTGACGCAGACTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGT CAGAGTGTTAGCAGCAGTTAC TTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTAT GGTGCATCC AGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGT CAGCAGTATGTTGGCTTAACAGGGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAAC SARS-CoV-2 S2E13-v1 mAb VH (aa) 409 QVQLVQSGTEVKKPGASVKVSCKAS GYTFISYG ISWVRQAPGQGLEWMGW ISPYNGNT HYAKRVQGRVTMTTDTSTNTSYMELRSLRSDDTAVYYCARDGELLGWFDPWGQGTLVTVSS SARS-CoV-2 S2E13-v1 mAb CDRH1 (aa) 410 GYTFISYG SARS-CoV-2 S2E13-v1 mAb CDRH2 (aa) 411 ISPYNGNT SARS-CoV-2 S2E13-v1 mAb CDRH3 (aa) 412 ARDGELLGWFDP SARS-CoV-2 S2E13-v1 mAb VL (aa) 413 HTELTQPASVSGSPGQSITISCTGT SSDVGNYNL VSWYQQHPGKAPKLMIY AGT KRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC CSYAGSSTWVFGGGTKLTVL SARS-CoV-2 S2E13-v1 mAb CDRL1 (aa) 414 SSDVGNYNL SARS-CoV-2 S2E13-v1 mAb CDRL2 (aa) 415 AGT SARS-CoV-2 S2E13-v1 mAb CDRL3 (aa) 416 CSYAGSSTWV SARS-CoV-2 S2E13-v1 mAb VH (nt) 417 CAGGTGCAGCTGGTGCAGTCTGGAACTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGTTACACCTTTATCAGCTATGGT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAGCCCTTACAATGGTAACACA CATTATGCAAAGAGGGTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAACACATCCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGAGATGGAGAACTCCTCGGCTGGTTCGATCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2E13-v1 mAb VL (nt) 418 CACACTGAGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACC AGCAGTGATGTTGGGAATTATAACCTT GTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTAT GCGGGCACT AAGCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGAGGCTGACTATTACTGC TGCTCATATGCAGGTAGTAGCACTTGGGTG TTCGGCGGAGGGACCAAGCTGACCGTCCTAG SARS-CoV-2 S2E14-v1 mAb VH (aa) 419 EVQLVESGGGVVQPGRSLRLSCAAS GFTFSSYA MHWVRQAPGKGLEWVTV ISSDGSNK YYAESVKGRFTISRDNSKNTLYLQMNSLRAEDTALYYCARDLPVIVATMWHYYNGMDVWGQGTTVTVSS SARS-CoV-2 S2E14-v1 mAb CDRH1 (aa) 420 GFTFSSYA SARS-CoV-2 S2E14-v1 mAb CDRH2 (aa) 421 ISSDGSNK SARS-CoV-2 S2E14-v1 mAb CDRH3 (aa) 422 ARLDPVIVATMWHYYNGMDV SARS-CoV-2 S2E14-v1 mAb VL (aa) 423 DIRMTQSPSSVSASVGDRVTITCRAS EGISSW LGWYQQKPGKAPKLLIY GAS SLQSGVPSRFSGSGFGTDFTLTISSLQPEDFATYYCQQAKSFPITFGQGTRLEIK SARS-CoV-2 S2E14-v1 mAb CDRL1 (aa) 424 EGISSW SARS-CoV-2 S2E14-v1 mAb CDRL2 (aa) 425 GAS SARS-CoV-2 S2E14-v1 mAb CDRL3 (aa) 426 QQAKSFPIT SARS-CoV-2 S2E14-v1 mAb VH (nt) 427 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCACCTTCAGTAGCTATGCT ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACAGTT ATTTCATCTGATGGAAGCAATAAA TACTACGCGGAGTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTCTATATTACTGT GCGAGAGACCTTCCTGTTATAGTGGCTACGATGTGGCACTACTATAACGGAATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCG SARS-CoV-2 S2E14-v1 mAb VL (nt) 428 GACATCCGGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGT GAAGGTATTAGCAGCTGG TTAGGCTGGTATCAGCAGAAACCAGGGAAGGCCCCTAAACTCCTGATCTAC GGTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATTTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAGCCTGAAGATTTTGCAACTTACTATTGT CAACAGGCTAAGAGTTTCCCGATCACC TTCGGCCAAGGGACACGACTGGAGATTAAAC SARS-CoV-2 S2K4-v1 mAb VH (aa) 429 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY MHWVRQAPGQGLEWMGW INPNSGGT NYTQKFQGWVTMTRDTSISTAYMELSRLSSDDTAVYYC ARDLAYSYVTGAFDI WGHGTMVTVSS SARS-CoV-2 S2K4-v1 mAb CDRH1 (aa) 430 GYTFTGYY SARS-CoV-2 S2K4-v1 mAb CDRH2 (aa) 431 INPNSGGT SARS-CoV-2 S2K4-v1 mAb CDRH3 (aa) 432 ARDLAYSYVTGAFDI SARS-CoV-2 S2K4-v1 mAb VH (nt) 433 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTAACAGTGGTGGCACA AACTATACACAGAAGTTTCAGGGCTGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCCTACATGGAGCTGAGCAGGCTGAGCTCTGACGACACGGCCGTGTATTACTGT GCGAGAGATCTCGCATACAGCTATGTCACGGGGGCTTTTGATATC TGGGGCCACGGGACAATGGTCACCGTCTCTTCAG SARS-CoV-2 S2X193-v1 mAb VH (aa) 434 EVHLVESGGGLVQPGSLRLSCAAS GIIVSRNY MSWVRQAPGKGLEWVSV IYSGGST FYADSVKGRFTISRDNSKNTLYLQMNSLRAGDTAVYYCARDMMNDAFDIWGQGTMVTVSS SARS-CoV-2 S2X193-v1 mAb CDRH1 (aa) 435 GIIVSRNY SARS-CoV-2 S2X193-v1 mAb CDRH2 (aa) 436 IYSGGST SARS-CoV-2 S2X193-v1 mAb CDRH3 (aa) 437 ARDMMNDAFDI SARS-CoV-2 S2X193-v1 mAb VH (aa) 438 DIQMTQSPSSLSASVGDRVTITCRAS QGISSY LAWYQQKPGKAPKLLIY SAS TLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPPEVTFGQGTRLEIK SARS-CoV-2 S2X193-v1 mAb CDRL1 (aa) 439 QGISSY SARS-CoV-2 S2X193-v1 mAb CDRL2 (aa) 440 SAS SARS-CoV-2 S2X193-v1 mAb CDRL3 (aa) 441 QQLNSYPPEVT SARS-CoV-2 S2X193-v1 mAb VH (nt) 442 GAGGTGCATCTGGTGGAGTCTGGGGGAGGTTTGGTCCAGCCGGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGAATCATCGTCAGTAGGAATTAC ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTT ATTTATAGCGGTGGTAGTACA TTCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCTGGGGACACGGCTGTGTATTACTGT GCGAGGGATATGATGAATGATGCTTTTGATATC TGGGGCCAAGGGACAATGGTCACCGTCTCTTCAG SARS-CoV-2 S2X193-v1 mAb VL (nt) 443 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGT CAGGGCATTAGCAGTTAT TTAGCCTGGTATCAGCAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT TCTGCATCC ACTTTGCAAAGTGGGGTCCCATCGAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGT CAACAGCTTAATAGTTACCCTCCGGAGGTCACC TTCGGCCAAGGGACACGACTGGAGATTAAAC SARS-CoV-2 S2X195-v1 mAb VH (aa) 444 EVHLVQSGAEVKKPGASVKVSCKAS GYTFTDYY MHWVRQAPGQGLEWMGW INPKIGGT NYAQKFQGRVTMTRDTSINTAYMELSRLRSDDTAVYYC AKDLQPSYCTDGVCWPDDAFDI WGQGTMVTVSS SARS-CoV-2 S2X195-v1 mAb CDRH1 (aa) 445 GYTFTDYY SARS-CoV-2 S2X195-v1 mAb CDRH2 (aa) 446 INPKIGGT SARS-CoV-2 S2X195-v1 mAb CDRH3 (aa) 447 AKDLQPSYCTDGVCWPDDAFDI SARS-CoV-2 S2X195-v1 mAb VL (aa) 448 AIRMTQTPLSLSVTPGQPASISCKSS QSLLHSDGKTY LYWYLQKPGQSPQLLIY EVS NRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQSIQLPPTFGQGTKVEIK SARS-CoV-2 S2X195-v1 mAb CDRL1 (aa) 449 QSLLHSDGKTY SARS-CoV-2 S2X195-v1 mAb CDRL2 (aa) 450 EVS SARS-CoV-2 S2X195-v1 mAb CDRL3 (aa) 451 MQSIQLPPT SARS-CoV-2 S2X195-v1 mAb VH (nt) 452 GAGGTGCATCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGACTACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTAAGATTGGTGGCACA AACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAACACAGCCTACATGGAACTGAGCAGGCTGAGATCTGACGACACGGCCGTATATTACTGT GCGAAAGATCTACAACCTTCATATTGTACTGATGGTGTATGCTGGCCCGATGATGCTTTTGATATC TGGGGCCAAGGGACAATGGTCACCGTCTCTTCAG SARS-CoV-2 S2X195-v1 mAb VL (nt) 453 GCCATCCGGATGACCCAGACTCCACTCTCTCTGTCCGTCACCCCTGGACAGCCGGCCTCCATCTCCTGCAAGTCTAGT CAGAGCCTCCTGCATAGTGATGGAAAGACCTAT TTGTATTGGTACCTGCAGAAGCCAGGCCAGTCTCCACAGCTCCTGATCTAT GAAGTTTCC AACCGCTTCTCTGGAGTGCCAGATAGGTTCAGTGGCAGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGGTGGAGGCTGAGGATGTTGGGGTTTATTACTGC ATGCAAAGTATACAGCTTCCTCCGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAAC SARS-CoV-2 S2X219-v1 mAb VH (aa) 454 EVQLVESGGGLIQPGGSLRLSCAAT GITVSRNY INWVRQAPGKGLEWVSI IYSGGTT YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDLNVVGGFDI WGQGTMVTVSS SARS-CoV-2 S2X219-v1 mAb CDRH1(aa) 455 GITVSRNY SARS-CoV-2 S2X219-v1 mAb CDRH2 (aa) 456 IYSGGTT SARS-CoV-2 S2X219-v1 mAb CDRH3 (aa) 457 ARDLNVVGGFDI SARS-CoV-2 S2X219-v1 mAb VL (aa) 458 EIVMTQSPGTLSLSPGERATLSCRAS QSISSSY LAWYQQKPGQAPRLLIY GAS SRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPPITFGQGTRLEIK SARS-CoV-2 S2X219-v1 mAb CDRL1 (aa) 459 QSISSSY SARS-CoV-2 S2X219-v1 mAb CDRL2 (aa) 460 GAS SARS-CoV-2 S2X219-v1 mAb CDRL3 (aa) 461 QQYGSSPPIT SARS-CoV-2 S2X219-v1 mAb VH (nt) 462 GAGGTGCAGCTGGTGGAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCACT GGGATCACCGTCAGTAGGAACTAC ATAAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAATT ATTTATAGCGGTGGTACTACA TACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGT GCGAGAGATTTAAACGTAGTGGGTGGTTTTGATATC TGGGGCCAAGGGACAATGGTCACCGTCTCTTCAG SARS-CoV-2 S2X219-v1 mAb VL (nt) 463 GAAATAGTGATGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGT CAGAGTATTAGCAGCAGCTAC TTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTAT GGTGCATCC AGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGT CAGCAGTATGGTAGCTCACCTCCGATCACC TTCGGCCAAGGGACACGACTGGAGATTAAAC SARS-CoV-2 S2X244-v1 mAb VH (aa) 464 QVQLVQSGTEVKKPGSSVKVSCKASGGTFSTFSINWVRQAPGQGLEWMGRIIPILKIADYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCAREAGFFEEYGSGSSGLDPWGQGTLVTVSS _ _ SARS-CoV-2 S2X244-v1 mAb CDRH1 (aa) 465 GGTFSTFS SARS-CoV-2 S2X244-v1 mAb CDRH2 (aa) 466 IIPILKIA SARS-CoV-2 S2X244-v1 mAb CDRH3 (aa) 467 AREAGFFEEYGSGSSGLDP SARS-CoV-2 S2X244-v1 mAb VL (aa) 468 EIVLTQSPLSLPVTPGEPASISCRSN LSLLHSNGYNY LDWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFILKISRVEAEDVGVYYC MQALQTPR FGGGTKVEIK SARS-CoV-2 S2X244-v1 mAb CDRL1 (aa) 469 LSLLHSNGYNY SARS-CoV-2 S2X244-v1 mAb CDRL2 (aa) 470 LGS SARS-CoV-2 S2X244-v1 mAb CDRL3 (aa) 471 MQALQTPR SARS-CoV-2 S2X244-v1 mAb VH (nt) 472 CAGGTCCAGCTGGTGCAATCTGGGACTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCT GGAGGCACCTTCAGCACCTTTAGT ATCAACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAAGG ATCATCCCTATCCTTAAAATAGCA GACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACAAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGT GCGAGAGAGGCAGGCTTCTTCGAGGAGTATGGTTCGGGGAGTTCAGGGCTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X244-v1 mAb VL (nt) 473 GAAATTGTGTTGACACAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAAT CTGAGTCTCCTGCATAGTAATGGATACAACTAT TTGGATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTAT TTGGGTTCT AATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTATACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGC ATGCAAGCTCTCCAAACTCCTCGT TTCGGCGGAGGGACCAAGGTGGAGATCAAAC SARS-CoV-2 S2X246-v1 mAb VH (aa) 474 QVQLVESGGGLVQPGSLRLSCAAS GFTFSIYE MNWVRQAPGKGLEWVSY ITSGGHTI FYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYC ASNPSSGYFFDYWGQGTLVTVSS SARS-CoV-2 S2X246-v1 mAb CDRH1 (aa) 475 GFTFSIYE SARS-CoV-2 S2X246-v1 mAb CDRH2 (aa) 476 ITSGGHTI SARS-CoV-2 S2X246-v1 mAb CDRH3 (aa) 477 ASNPSSGYFFDY SARS-CoV-2 S2X246-v1 mAb VL (aa) 478 AIRMTQSPSTLSASVGDRVTITCRAS QSISSW LAWYQQKPGKAPKLLIY KAS SLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPYTFGQGTKLDIK SARS-CoV-2 S2X246-v1 mAb CDRL1 (aa) 479 QSISSW SARS-CoV-2 S2X246-v1 mAb CDRL2 (aa) 480 KAS SARS-CoV-2 S2X246-v1 mAb CDRL3 (aa) 481 QQYNSYPYT SARS-CoV-2 S2X246-v1 mAb VH (nt) 482 CAGGTACAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGAGGGTCCCTGAGGCTCTCCTGTGCAGCCTCT GGATTCACCTTCAGTATTTATGAA ATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTTTCATAC ATTACTAGTGGTGGTCATACCATA TTCTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGCGAGCCGAGGACACGGCTGTTTATTACTGT GCGAGCAACCCGAGTAGTGGTTATTTTTTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X246-v1 mAb VL (nt) 483 GCCATCCGGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGT CAGAGTATTAGTAGCTGG TTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT AAGGCGTCT AGTTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGC CAACAGTATAATAGTTATCCCTACACT TTTGGCCAGGGGACCAAGCTGGACATCAAAC SARS-CoV-2 S2X256-v1 mAb VH (aa) 484 EVQLVESGGGLIQPGGSLRLSCAAS GIIVSSNY MNWVRQAPGRGLEWVSV IYSGGST FYADSVKGRFTISRDSSKNTLYLQMNGLRAEDTAVYYC ARDLGESGMDV WGQGTTVTVSS SARS-CoV-2 S2X256-v1 mAb CDRH1 (aa) 485 GIIVSSNY SARS-CoV-2 S2X256-v1 mAb CDRH2 (aa) 486 IYSGGST SARS-CoV-2 S2X256-v1 mAb CDRH3 (aa) 487 ARDLGESGMDV SARS-CoV-2 S2X256-v1 mAb VL (aa) 488 AIRMTQSPSSVSASVGDRVTITCRAS QGISSW LAWYQQKPGKAPKLLIS AAS NLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPRFGPGTKVDIK SARS-CoV-2 S2X256-v1 mAb CDRL1 (aa) 489 QGISSW SARS-CoV-2 S2X256-v1 mAb CDRL2 (aa) 490 AAS SARS-CoV-2 S2X256-v1 mAb CDRL3 (aa) 491 QQANSFPR SARS-CoV-2 S2X256-v1 mAb VH (nt) 492 GAGGTGCAGCTGGTGGAGTCTGGAGGGGGCTTGATCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGGATCATCGTCAGTAGCAACTAC ATGAACTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAGTGGGTCTCAGTT ATTTATAGCGGTGGTAGCACA TTCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAGTTCCAAGAACACACTGTATCTTCAAATGAACGGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGT GCGAGAGATCTGGGAGAGAGCGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2X256-v1 mAb VL (nt) 493 GCCATCCGGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGT CAGGGTATTAGCAGCTGG TTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTCT GCTGCATCC AATTTGCAAAGTGGGGTCCCATCTAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGT CAACAGGCTAACAGTTTCCCTCGG TTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2X269-v1 mAb VH (aa) 494 EVQLVESGGGVVQPGRSLRLSCAAS GFAFRIYG MHWVRQAPGKGLEWVAL IWFDGNNK YYADSVKGRFTISRDSSKNTLFLQMNSLRAEDTALYYC ARAMCPGETGNLLGICYAPDYWGQGTLVTVSS SARS-CoV-2 S2X269-v1 mAb CDRH1 (aa) 495 GFAFRIYG SARS-CoV-2 S2X269-v1 mAb CDRH2 (aa) 496 IWFDGNNK SARS-CoV-2 S2X269-v1 mAb CDRH3 (aa) 497 ARAMCPGETGNLLGICYAPDY SARS-CoV-2 S2X269-v1 mAb VL (aa) 498 QSALTQPPSASGTPGQRVTISCSGSTSNIGSNHVCWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDRLSGWVFGGGTKLTVL _ _ SARS-CoV-2 S2X269-v1 mAb CDRL1 (aa) 499 TSNIGSNH SARS-CoV-2 S2X269-v1 mAb CDRL2 (aa) 500 SNN SARS-CoV-2 S2X269-v1 mAb CDRL3 (aa) 501 AAWDDRLSGWV SARS-CoV-2 S2X269-v1 mAb VH (nt) 502 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCT GGATTCGCCTTCAGAATCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCACTT ATATGGTTTGATGGAAATAATAAA TACTATGCCGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAGTTCCAAGAACACACTGTTTCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTCTGTATTACTGT GCGAGAGCGATGTGCCCAGGCGAAACGGGAAATCTTCTGGGTATCTGCTACGCCCCTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X269-v1 mAb VL (nt) 503 CAGTCTGCCCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGTTCTGGAAGC ACCTCCAACATCGGAAGTAATCAT GTATGCTGGTACCAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTAT AGTAATAAT CAACGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCGGTCCGAGGATGAGGCTGATTATTACTGT GCAGCATGGGATGACAGACTGAGTGGCTGGGTG TTCGGCGGAGGGACCAAGCTGACCGTCCTAG SARS-CoV-2 S2X278-v1 mAb VH (aa) 504 QVRLQESGPGLVKPSETLSLTCAVS GYSISSGYY WGWIRQPPGKGLEWIGS IYESGST YNNPSLKSRVTMSVDTSKNQFSLKLTSVTAADTAVYYC ARDLWEGDYYRVGDYWGQGTLVTVSS SARS-CoV-2 S2X278-v1 mAb CDRH1 (aa) 505 GYSISSGYY SARS-CoV-2 S2X278-v1 mAb CDRH2 (aa) 506 IESGST SARS-CoV-2 S2X278-v1 mAb CDRH3 (aa) 507 ARDLWEGDYYRVGDY SARS-CoV-2 S2X278-v1 mAb VL (aa) 508 QSVLTQPPSVSAAPGQKVTISCSGS SSNVGNNY VSWYQQLPGTAPKLLIY DNT KRPSWIPDRFSGSKSGTSATLDITGLQTGDEADYYCGTWDSSLSVVFGGGTKLTVL SARS-CoV-2 S2X278-v1 mAb CDRL1 (aa) 509 SSNVGNNY SARS-CoV-2 S2X278-v1 mAb CDRL2 (aa) 510 DNT SARS-CoV-2 S2X278-v1 mAb CDRL3 (aa) 511 GTWDSSLSVV SARS-CoV-2 S2X278-v1 mAb VH (nt) 512 CAGGTGCGGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCGCTGTCTCT GGTTACTCCATCAGCAGTGGTTACTAC TGGGGCTGGATCCGGCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGAGT ATCTATGAGAGTGGGAGCACC TACAACAACCCGTCCCTCAAGAGTCGAGTCACCATGTCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGACCTCTGTGACCGCCGCAGACACGGCCGTATATTACTGT GCGAGAGACCTCTGGGAAGGTGACTACTACCGAGTGGGGGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X278-v1 mAb VL (nt) 513 CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTGCGGCCCCAGGACAGAAGGTCACCATCTCCTGCTCTGGAAGC AGCTCCAACGTTGGGAATAATTAT GTATCCTGGTACCAGCAGCTCCCAGGAACAGCCCCCAAACTCCTCATTTAT GACAATACT AAGCGACCCTCATGGATTCCTGACCGATTCTCTGGCTCCAAGTCTGGCACGTCAGCCACCCTGGACATCACCGGACTCCAGACTGGGGACGAGGCCGATTATTACTGC GGAACATGGGATAGCAGTCTGAGTGTTGTC TTCGGCGGAGGGACCAAGCTGACCGTCCTAG SARS-CoV-2 S2M7-v1 mAb VH (aa) 514 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTSYY MHWVRQAPGQGLEWMGI INPSGTST SYAQKFQGRVTMTRDTSTSTVYLDLSSLRSGDTAVYYC ATGSWELPSYFDY WGQGTLITVSS SARS-CoV-2 S2M7-v1 mAb CDRH1 (aa) 515 GYTFTSYY SARS-CoV-2 S2M7-v1 mAb CDRH2 (aa) 516 INPSGTST SARS-CoV-2 S2M7-v1 mAb CDRH3 (aa) 517 ATGSWELPSYFDY SARS-CoV-2 S2M7-v1 mAb VL (aa) 518 DIVMMQSPGTLSLSPGERATLSCRAS QSIYSSY LAWYQQKPGQAPRLLIS GAS SRATGIPDRFSGSGSGTDFTLTISRLEPADFAVYYCQQYGSSPPTFGQGTKVEIK SARS-CoV-2 S2M7-v1 mAb CDRL1 (aa) 519 QSIYSSY SARS-CoV-2 S2M7-v1 mAb CDRL2 (aa) 520 GAS SARS-CoV-2 S2M7-v1 mAb CDRL3 (aa) 521 QQYGSSPPT SARS-CoV-2 S2M7-v1 mAb VH (nt) 522 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTTTCCTGCAAGGCATCT GGATACACCTTCACCAGCTACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAATA ATCAACCCTAGTGGTACTAGCACA AGCTACGCACAGAAGTTCCAGGGCAGAGTCACTATGACCAGGGACACGTCCACGAGCACAGTCTACTTGGACCTGAGCAGCCTGAGATCTGGTGACACGGCCGTGTATTACTGT GCGACCGGGTCGTGGGAGCTACCTTCCTACTTTGACTAC TGGGGCCAGGGAACCCTGATCACCGTCTCCTCAG SARS-CoV-2 S2M7-v1 mAb VL (nt) 523 GACATCGTGATGATGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGT CAGAGTATTTACAGCAGCTAT TTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTCT GGTGCATCC AGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGCGGATTTTGCAGTGTATTACTGT CAGCAGTATGGTAGCTCACCTCCGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAAC SARS-CoV-2 S2M11-v1 mAb VH (aa) 524 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY MHWVRQAPGQGLEWMGW INPISSGT SYAQTFQGRVTMTSDTSITTAYMELSRLRSDDTAVYYC ARAAPFYDFWSGYSYFDY WGQGTLVTVSS SARS-CoV-2 S2M11-v1 mAb CDRH1 (aa) 525 GYTFTGYY SARS-CoV-2 S2M11-v1 mAb CDRH2 (aa) 526 INPISSGT SARS-CoV-2 S2M11-v1 mAb CDRH3 (aa) 527 ARAAPFYDFWSGYSYFDY SARS-CoV-2 S2M11-v1 mAb VL (aa) 528 EIVMMQSPGTLSLSPGERATLSCRAS QSVSSSY LAWYQQKPGQAPRLLIY GAS SRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSAWTFGQGTKVEIK SARS-CoV-2 S2M11-v1 mAb CDRL1 (aa) 529 QSVSSSY SARS-CoV-2 S2M11-v1 mAb CDRL2 (aa) 530 GAS SARS-CoV-2 S2M11-v1 mAb CDRL3 (aa) 531 QQYGSSAWT SARS-CoV-2 S2M11-v1 mAb VH (nt) 532 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTAT ATGCACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTATCAGTAGTGGCACA AGCTATGCACAGACATTTCAGGGCAGGGTCACCATGACCAGTGACACGTCCATCACCACAGCCTACATGGAGCTCAGCAGGCTGAGATCTGACGACACGGCCGTATATTACTGT GCGAGAGCAGCCCCGTTTTACGATTTTTGGAGTGGTTATTCTTACTTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2M11-v1 mAb VL (nt) 533 GAAATAGTGATGATGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGT CAGAGTGTTAGCAGCAGCTAC TTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTAT GGTGCATCC AGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGT CAGCAGTATGGTAGCTCAGCGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAAC SARS-CoV-2 S2M16-v1 mAb VH (aa) 534 EVQLVESGGGMVLPGRSLRLSCAAS GFTFSNYA MHWVRQAPGKGLEWVAV ISYDGSTK YFADSVKGRFTISRDTSKNTLYLQMNSLRAEDTAVYYC AKDSETCSSFTCYCDY WGRGTLVTVSS SARS-CoV-2 S2M16-v1 mAb CDRH1 (aa) 535 GFTFSNYA SARS-CoV-2 S2M16-v1 mAb CDRH2 (aa) 536 ISYDGSTK SARS-CoV-2 S2M16-v1 mAb CDRH3 (aa) 537 AKDSETCSSFTCYCDY SARS-CoV-2 S2M16-v1 mAb VL (aa) 538 DIVLTQSPDSLAVSLGERATINCKSS QSVLYSSNNKNY LAWYQQKPGQPPKLLIY WAS TRESGVPDRFSGSGSGTDFTLTIGSLQAEDVAVYYCQQYYNTPFTFGPGTKVDIK SARS-CoV-2 S2M16-v1 mAb CDRL1 (aa) 539 QSVLYSSNNKNY SARS-CoV-2 S2M16-v1 mAb CDRL2 (aa) 540 WAS SARS-CoV-2 S2M16-v1 mAb CDRL3 (aa) 541 QQYYNTPFT SARS-CoV-2 S2M16-v1 mAb VH (nt) 542 GAGGTGCAACTGGTGGAGTCTGGGGGAGGCATGGTCCTGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCACCTTCAGTAACTATGCC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTT ATATCGTATGATGGAAGTACTAAA TACTTTGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACACTTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGT GCGAAAGATTCAGAGACTTGTAGTAGTTTCACCTGCTATTGCGACTAC TGGGGCCGGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2M16-v1 mAb VL (nt) 543 GATATTGTGCTGACTCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCATCAACTGCAAGTCCAGC CAGAGTGTTTTATACAGCTCCAACAATAAGAACTAC TTAGCTTGGTACCAGCAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTAC TGGGCATCT ACCCGGGAATCCGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCGGCAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGT CAGCAATATTATAATACTCCCTTCACT TTCGGCCCTGGGACCAAAGTGGATATCAAAC SARS-CoV-2 S2M28-v1 mAb VH (aa) 544 EVQLVESGGGVVQPGRSLRLSCAAS GFTFSSYG MHWVRQAPGKGLEWVTV IWYDGSNR YYADSVKGRFTISRDNSKNTLYLQMDSLRAEDTAVYYC ARAVAGEWYFDY WGQGTLVTVSS SARS-CoV-2 S2M28-v1 mAb CDRH1 (aa) 545 GFTFSSYG SARS-CoV-2 S2M28-v1 mAb CDRH2 (aa) 546 IWYDGSNR SARS-CoV-2 S2M28-v1 mAb CDRH3 (aa) 547 ARAVAGEWYFDY SARS-CoV-2 S2M28-v1 mAb VL (aa) 548 SYELTQPPSVSVSPGQTARITCSGD ALAKHY AYWYRQKPGQAPVLVIY KDS ERPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCQSADSIGSSWVFGGGTKLTVL SARS-CoV-2 S2M28-v1 mAb CDRL1 (aa) 549 ALAKHY SARS-CoV-2 S2M28-v1 mAb CDRL2 (aa) 550 KDS SARS-CoV-2 S2M28-v1 mAb CDRL3 (aa) 551 QSADSIGSSWV SARS-CoV-2 S2M28-v1 mAb VH (nt) 552 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACTCTCCTGTGCAGCGTCT GGATTCACCTTCAGTAGCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGACAGTT ATTTGGTATGATGGAAGTAATCGA TACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGGACAGCCTGAGAGCCGAGGACACGGCTGTTTATTACTGT GCGAGAGCAGTGGCCGGGGAATGGTACTTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2M28-v1 mAb VL (nt) 553 TCCTATGAGCTGACACAGCCACCCTCGGTGTCAGTGTCCCCAGGACAGACGGCCAGGATCACCTGCTCCGGAGAT GCATTGGCAAAACACTAT GCTTATTGGTACCGGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTGATATAT AAAGACAGT GAGAGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAGCTCAGGGACAACAGTCACGTTGACCATCAGTGGAGTCCAGGCAGAAGACGAGGCTGACTATTACTGT CAATCAGCAGACAGCATTGGTAGTTCTTGGGTG TTCGGCGGAGGGACCAAGCTGACCGTCCTAG SARS-CoV-2 S2L49-v1 mAb VH (aa) 554 EVQLLESGGGVVQPGGSLRLSCAAS GFNFSSYG MHWVRQAPGKGLEWVAF MRYDETNK YYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC AKDRLLGGPYYDSIGLDY WGQGTLVTVSS SARS-CoV-2 S2L49-v1 mAb CDRH1 (aa) 555 GFNFSSYG SARS-CoV-2 S2L49-v1 mAb CDRH2 (aa) 556 MRYDETNK SARS-CoV-2 S2L49-v1 mAb CDRH3 (aa) 557 AKDRLLGGPYYDSIGLDY SARS-CoV-2 S2L49-v1 mAb VL (aa) 558 DIVMTQSPSSVSASVGDRVTITCRAS QGISSW LAWYQQKPGKAPKLLIY TAS SLQSGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQGYSFPYTFGQGTKLEIK SARS-CoV-2 S2L49-v1 mAb CDRL1 (aa) 559 QGISSW SARS-CoV-2 S2L49-v1 mAb CDRL2 (aa) 560 TAS SARS-CoV-2 S2L49-v1 mAb CDRL3 (aa) 561 QQGYSFPYT SARS-CoV-2 S2L49-v1 mAb VH (nt) 562 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCGTCT GGATTCAACTTCAGTAGCTATGGC ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCATTT ATGCGGTATGATGAAACTAATAAA TACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGT GCGAAAGATCGGCTATTAGGAGGTCCATATTATGATAGCATTGGGCTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2L49-v1 mAb VL (nt) 563 GATATTGTGATGACTCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGT CAGGGTATTAGCAGCTGG TTAGCCTGGTATCAGCAGAAACCAGGTAAAGCCCCTAAGCTCTTGATCTAT ACTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGAATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGT CAACAGGGTTACAGTTTCCCGTACACT TTTGGCCAGGGGACCAAGCTGGAGATCAAAC SARS-CoV-2 S2D65-v1 mAb VH (aa) 564 EVQLVESGGGLAQPGRSLRLSCAVS GFSFDDYA MHWVRQVPGKGLEWVSG ISWNSGNI GYADSAKGRFTISRDNAKNSLYLQMNSLRPEDTALYYC VKDKHYDSSGYVVNGFDYWGQGTLVTVSP SARS-CoV-2 S2D65-v1 mAb CDRH1 (aa) 565 GFSFDDYA SARS-CoV-2 S2D65-v1 mAb CDRH2 (aa) 566 ISWNSGNI SARS-CoV-2 S2D65-v1 mAb CDRH3 (aa) 567 VKDKHYDSSGYVVNGFDY SARS-CoV-2 S2D65-v1 mAb VL (aa) 568 DIQLTQSPSFLSASVGDRVTITCRAS QDISSY LAWYQQKPGKAPKLLIY AAS TLQSGVPSRFSGSGSGTEFTLTIRSLQPEDFATYYC QQLHSYPAT FGQGTKVEIK SARS-CoV-2 S2D65-v1 mAb CDRL1 (aa) 569 QDISSY SARS-CoV-2 S2D65-v1 mAb CDRL2 (aa) 570 AAS SARS-CoV-2 S2D65-v1 mAb CDRL3 (aa) 571 QQLHSYPAT SARS-CoV-2 S2D65-v1 mAb VH (nt) 572 GAGGTGCAGCTGGTGGAGTCGGGGGGAGGCTTGGCACAGCCTGGCAGGTCCCTGAGACTCTCCTGTGCAGTCTCT GGATTCAGCTTTGATGATTATGCC ATGCACTGGGTCCGGCAAGTTCCAGGGAAGGGCCTGGAGTGGGTCTCAGGT ATTAGTTGGAATAGTGGTAACATA GGCTATGCGGACTCTGCGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCTGAGACCTGAGGACACGGCCTTGTATTACTGT GTAAAAGATAAACATTATGATAGTAGTGGTTACGTAGTAAATGGATTTGACTAC TGGGGCCAGGGAACCCTGGTCACCGTCTCCCCAG SARS-CoV-2 S2D65-v1 mAb VL (nt) 573 GACATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCCAGT CAGGACATTAGCAGTTAT TTGGCCTGGTATCAGCAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT GCTGCATCC ACTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCCGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGT CAACAGCTTCACAGTTACCCTGCGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAAC SARS-CoV-2 S2D97-v1 mAb VH (aa) 574 QITLKESGPTLVKPTQTLTLTCSFS GFSLTTSGVG VAWIRQPPGKALEWLALIYWDDDKRYSPTLRSRLTITKDTSKNQVVLTMTNMDPVDTATYYCALHQIMTVFDLWGRGALVTVSS SARS-CoV-2 S2D97-v1 mAb CDRH1 (aa) 575 GFSLTTSGVG SARS-CoV-2 S2D97-v1 mAb CDRH2 (aa) 576 IYWDDDK SARS-CoV-2 S2D97-v1 mAb CDRH3 (aa) 577 ALHQIMTVFDL SARS-CoV-2 S2D97-v1 mAb VL (aa) 578 QSVLTQPASVSGSPGQSITISCTGT SSDVGDYNY VSWYQHHPGKAPKLMIY QVT NRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC TSYTTSSTLVEFGGGTKLTVL SARS-CoV-2 S2D97-v1 mAb CDRL1 (aa) 579 SSDVGDYNY SARS-CoV-2 S2D97-v1 mAb CDRL2 (aa) 580 QVT SARS-CoV-2 S2D97-v1 mAb CDRL3 (aa) 581 TSYTTSSTLVE SARS-CoV-2 S2D97-v1 mAb VH (nt) 582 CAGATCACCTTGAAGGAGTCTGGTCCTACCCTGGTGAAACCCACACAGACCCTCACGCTGACCTGCAGTTTCTCT GGGTTCTCACTCACCACTAGTGGAGTGGGT GTGGCCTGGATCCGTCAGCCCCCAGGAAAGGCCCTGGAGTGGCTTGCACTC ATTTATTGGGATGATGACAAG CGCTACAGCCCAACTCTGAGGAGCAGGCTCACCATCACCAAGGACACCTCCAAGAACCAGGTGGTCCTTACAATGACCAACATGGACCCTGTGGACACAGCCACATATTACTGT GCACTACACCAGATTATGACGGTCTTCGATCTC TGGGGCCGTGGCGCCCTGGTCACTGTCTCCTCAG SARS-CoV-2 S2D97-v1 mAb VL (nt) 583 CAGTCTGTGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGCCAGTCGATCACCATCTCCTGCACTGGAACC AGCAGTGACGTTGGTGATTATAACTAT GTGTCCTGGTACCAACACCACCCAGGCAAAGCCCCCAAACTCATGATTTAT CAGGTCACT AATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTACTGC ACTTCCTATACAACCAGTAGTACTCTCGTGGAA TTCGGCGGAGGGACCAAGTTGACCGTCTTAG SARS-CoV-2 S2D106-v1 mAb VH (aa) 584 EVQLVQSGAEVKKPGSSVKVSCKASGGPFSSSA ISWVRQAPGQGLEWMGGIIPMVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYC ARDSRYCSGGSCYSVWFDPWGQGTLVTVSS SARS-CoV-2 S2D106-v1 mAb CDRH1 (aa) 585 GGPFSSSA SARS-CoV-2 S2D106-v1 mAb CDRH2 (aa) 586 IIPMVGTA SARS-CoV-2 S2D106-v1 mAb CDRH3 (aa) 587 ARDSRYCSGGSCYSVWFDP SARS-CoV-2 S2D106-v1 mAb VL (aa) 588 DIQLTQSPSSLSASVGDRVTITCRAS QSISSY LNWYQQKPGKAPKVLIY AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPRTFGQGTKVEMK SARS-CoV-2 S2D106-v1 mAb CDRL1 (aa) 589 QSISSY SARS-CoV-2 S2D106-v1 mAb CDRL2 (aa) 590 AAS SARS-CoV-2 S2D106-v1 mAb CDRL3 (aa) 591 QQSYSTPRT SARS-CoV-2 S2D106-v1 mAb VH (nt) 592 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTTTCCTGCAAGGCTTCT GGAGGCCCCTTCAGCAGCTCTGCT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGG ATCATCCCTATGGTAGGTACAGCA AACTATGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGT GCGAGAGATTCGCGCTATTGTAGTGGTGGTAGCTGCTACTCCGTCTGGTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2D106-v1 mAb VL (nt) 593 GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGT CAGAGCATTAGCAGCTAT TTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGGTCCTGATCTAT GCTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTCCAACCTGAAGATTTTGCAACTTACTACTGT CAACAGAGTTACAGTACCCCTCGAACG TTCGGCCAAGGGACCAAGGTGGAAATGAAAC SARS-CoV-2 S2X149-v1 mAb VH (aa) 594 QVQLVQSGADVKKPGASVKVSCKAS GYTFTGYF IHWVRQAPGQGLEWMGW INPISGGR NYTRKFQGRITMNRDTSITTAYMELSRLRSDDTAVYYC ARDSGGMDYGSGSYFSPPRYGMDVWGQGTTVTVSS SARS-CoV-2 S2X149-v1 mAb CDRH1 (aa) 595 GYTFTGYF SARS-CoV-2 S2X149-v1 mAb CDRH2 (aa) 596 INPISGGR SARS-CoV-2 S2X149-v1 mAb CDRH3 (aa) 597 ARDSGGMDYGSGSYFSPPRYGMDV SARS-CoV-2 S2X149-v1 mAb VL (aa) 598 QSVLTQPASVSGSPGQSITISCTGA SSDVGAYNF VSWYQQHPGKAPKLMIY EVS NRPSGVSNRFSGSKSGNTASLTISGLQAEDEAAYYC SSYTSSNTVVFGGGTSLTVL SARS-CoV-2 S2X149-v1 mAb CDRL1 (aa) 599 SSDVGAYNF SARS-CoV-2 S2X149-v1 mAb CDRL2 (aa) 600 EVS SARS-CoV-2 S2X149-v1 mAb CDRL3 (aa) 601 SSYTSSNTVV SARS-CoV-2 S2X149-v1 mAb VH (nt) 602 CAGGTGCAGCTGGTGCAGTCTGGGGCTGACGTGAAGAAGCCTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGATACACCTTCACCGGCTACTTT ATACACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTATCAGTGGTGGCAGA AACTATACACGGAAGTTTCAGGGCAGGATCACCATGAACAGGGACACGTCCATCACCACAGCCTACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGAGAGATTCGGGGGGGATGGACTATGGTTCGGGGAGTTATTTTTCCCCCCCCCGATACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA SARS-CoV-2 S2X149-v1 mAb VL (nt) 603 CAGTCTGTGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAGCC AGCAGTGACGTTGGTGCTTATAACTTT GTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTAT GAGGTCAGT AATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGCTTATTACTGC AGCTCATATACAAGCAGTAACACTGTGGTA TTCGGCGGAGGGACCAGCCTGACCGTCCTAG SARS-CoV-2 S2X179-v1 mAb VH (aa) 604 EVQLVESGGGLVQPGSLRLSCAAS GITVSSNY MTWVRQAPGKGLEWVSV IYSGGST FYADSVRGRFTISRDNSKNTLYLQMNSLRPDDTAVYYC ARDLNELGIDC WGQGTLVTVSS SARS-CoV-2 S2X179-v1 mAb CDRH1 (aa) 605 GITVSSNY SARS-CoV-2 S2X179-v1 mAb CDRH2 (aa) 606 IYSGGST SARS-CoV-2 S2X179-v1 mAb CDRH3 (aa) 607 ARDLNELGIDC SARS-CoV-2 S2X179-v1 mAb VL (aa) 608 DIVMTQTPSSVSASVGDRVTITCRAS QGISRW LAWYQQKPGKAPKLLIY AAS TLQSGVPSRFSGSGSGTDFTLTIRSLQPEDYATYYC QQANSFPFFGGGTKVEIK SARS-CoV-2 S2X179-v1 mAb CDRL1 (aa) 609 QGISRW SARS-CoV-2 S2X179-v1 mAb CDRL2 (aa) 610 AAS SARS-CoV-2 S2X179-v1 mAb CDRL3 (aa) 611 QQANSFPF SARS-CoV-2 S2X179-v1 mAb VH (nt) 612 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGTATCACCGTCAGTAGCAATTAT ATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATGGGTCTCAGTT ATTTATAGCGGTGGCAGCACA TTCTACGCAGACTCCGTGAGGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACCCTGTATCTTCAAATGAACAGCCTGAGACCTGACGACACGGCTGTGTATTACTGT GCGAGAGATCTGAACGAGCTGGGGATTGACTGC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2X179-v1 mAb VL (nt) 613 GATATTGTGATGACCCAGACTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCGGGCGAGT CAGGGTATTAGCCGCTGG TTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTAT GCTGCATCC ACTTTACAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGGAGCCTGCAGCCTGAAGATTATGCAACTTACTATTGT CAACAGGCTAACAGTTTCCCTTTT TTCGGCGGAGGGACCAAGGTGGAGATCAAAC SARS-CoV-2 S2H101-v1 mAb VH (aa) 614 EVHLVESGGGLVQPGSLRLSCAAS GFTFINYA MSWVRQAPGKGLEWVSA IGLSGGST NYADSVKGRFTISRDNSKNTLSLEMNNLRAEDTAVYYC TKGRGGYFDPFDPWGQGTLVTVSS SARS-CoV-2 S2H101-v1 mAb CDRH1 (aa) 615 GFTFINYA SARS-CoV-2 S2H101-v1 mAb CDRH2 (aa) 616 IGLSGGST SARS-CoV-2 S2H101-v1 mAb CDRH3 (aa) 617 TKGRGGYFDPFDP SARS-CoV-2 S2H101-v1 mAb VL (aa) 618 DIVMTQSPSSLSASVGDRVTITCRAS QSISSY LNWYQQIPGKAPNLLIH AAS SLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPPTFGQGTKLEIK SARS-CoV-2 S2H101-v1 mAb CDRL1 (aa) 619 QSISSY SARS-CoV-2 S2H101-v1 mAb CDRL2 (aa) 620 AAS SARS-CoV-2 S2H101-v1 mAb CDRL3 (aa) 621 QQSYSSPPT SARS-CoV-2 S2H101-v1 mAb VH (nt) 622 GAGGTGCATCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCACCTTTATCAACTATGCC ATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATGGGTCTCAGCT ATTGGTCTTAGTGGTGGTAGTACA AACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAACTCCAAGAACACGCTGTCTTTGGAAATGAACAACCTGCGAGCCGAGGACACGGCCGTATATTACTGT ACAAAAGGGAGGGGAGGATATTTTGACCCGTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAG SARS-CoV-2 S2H101-v1 mAb VL (nt) 623 GACATCGTGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTTGGGGACAGAGTCACCATCACTTGCCGGGCAAGT CAGAGCATTAGCAGCTAT TTAAATTGGTATCAGCAGATACCAGGGAAAGCCCCTAACCTCCTGATCCAT GCTGCATCC AGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGT CAGCAGAGTTACAGTTCCCCTCCCACT TTTGGCCAGGGGACCAAGCTGGAGATCAAAC Antibody 409_11_1_v2 VH 624 EVQLVQSGAEVKKPGSSVKVSCKASGGPFSSSA ISWVRQAPGQGLEWMGG IIPIVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYC ARDSRYCSGGSCYSVWFDPWGQGTLVTVSS Antibody 409_11_1_v2 CDRH2 625 IIPIVGTA Antibody 409_11_1_v3 VH 626 EVQLVQSGAEVKKPGSSVKVSCKASGGPFSSSA ISWVRQAPGQGLEWMGG IIPMVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYC ARDSRYCSGGSCYSVFFDPWGQGTLVTVSS Antibody 409_11_1_v3 CDRH3 627 ARDSRYCSGGSCYSVFFDP Antibody 409_11_1_v4 VH 628 EVQLVQSGAEVKKPGSSVKVSCKASGGPFSSSA ISWVRQAPGQGLEWMGG IIPIVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYC ARDSRYCSGGSCYSVFFDPWGQGTLVTVSS [ reserved ] 629 [ reserved ] Antibody 409_11_2_v1 VH 630 QITLKESGPTLVKPTQTLTLTCTFS GFSVTTSGVG VGWIRQPPGKALEYLAL IYWDDDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYC ARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v1 CDRH1 631 GFSVTTSGVG Antibody 409_11_2_v1 CDRH2 632 IYWDDDK Antibody 409_11_2_v1 CDRH3 633 ARHTIPSIFDY Antibody 409_11_2_v2 VH 634 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYFDDDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v2 CDRH2 635 IYFDDDK Antibody 409_11_2_v3 VH 636 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYDDDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v3 CDRH2 637 IYYDDDK Antibody 409_11_2_v4 VH 638 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYWEDDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v4 CDRH2 639 IYWEDDK Antibody 409_11_2_v5 VH 640 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYWNDDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v5 CDRH2 641 IYWNDDK Antibody 409_11_2_v6 VH 642 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYWDEDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_24_v6 CDRH2 643 IYWDEDK Antibody 409_11_2_v7 VH 644 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYWDNDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v7 CDRH2 645 IYWDNDK Antibody 409_11_2_v8 VH 646 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYFEDDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v8 CDRH2 647 IYFEDDK Antibody 409_11_2_v9 VH 648 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYFNDDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v9 CDRH2 649 IYFNDDK Antibody 409_11_2_v10 VH 650 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYEDDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v10 CDRH2 651 IYYEDDK Antibody 409_11_2_v11 VH 652 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYNDDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v11 CDRH2 653 IYYNDDK Antibody 409_11_2_v12 VH 654 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYFDEDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v12 CDRH2 655 IYFDEDK Antibody 409_11_2_v13 VH 656 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYFDNDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v13 CDRH2 657 IYFDNDK Antibody 409_11_2_v14 VH 658 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYDEDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v14 CDRH2 659 IYYDEDK Antibody 409_11_2_v15 VH 660 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYDNDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v15 CDRH2 661 IYYDNDK Antibody 409_11_2_v16 VH 662 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYWEEDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v16 CDRH2 663 IYWEEDK Antibody 409_11_2_v17 VH 664 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYWENDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v17 CDRH2 665 IYWENDK Antibody 409_11_2_v18 VH 666 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYWNEDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v18 CDRH2 667 IYWNEDK Antibody 409_11_2_v19 VH 668 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYWNNDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v19 CDRH2 669 IYWNNDK Antibody 409_11_2_v20 VH 670 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYFEEDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v20 CDRH2 671 IYFEEDK Antibody 409_11_2_v21 VH 672 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLALIYFENDKRYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v21 CDRH2 673 IYFENDK Antibody 409_11_2_v22 VH 674 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYFNEDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS S2X324_v22 CDRH2 675 IYFNEDK Antibody 409_11_2_v23 VH 676 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYFNNDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v23 CDRH2 677 IYFNNDK Antibody 409_11_2_v24 VH 678 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYEEDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v24 CDRH2 679 IYYEEDK Antibody 409_11_2_v25 VH 680 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYENDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2_v25 CDRH2 681 IYYENDK Antibody 409_11_2_v26 VH 682 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYNEDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS Antibody 409_11_2__v26 CDRH2 683 IYYNEDK Antibody 409_11_2_v27 VH 684 QITLKESGPTLVKPTQTLTLTCTFSGFSVTTSGVGVGWIRQPPGKALEYLAL IYYNNDK RYSTSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARHTIPSIFDYWGQGILVTVSS S2X324_v27 CDRH2 685 IYYNNDK Antibody 409_11_2 VL 686 QPVLTQPASVSGSPGQSITISCTAT SSDVGNYNY VSWYQHHPGKAPKLMIY EVS NRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYC SSYTSSSLLFGGGTKLTVL Antibody 409_11_2 CDRL1 687 SSDVGNYNY Antibody 409_11_2 CDRL2 688 EVS Antibody 409_11_2 CDRL3 689 SSYTSSSLL Antibody 409_11_2 VH (nt) 690 CAGATCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAAACCCACACAGACCCTCACGCTGACCTGCACCTTCTCT GGGTTCTCAGTCACTACTAGTGGAGTGGGT GTGGGCTGGATCCGTCAGCCCCCAGGAAAGGCCCTGGAGTACCTTGCACTC ATTTATTGGGATGATGATAAG CGCTACAGTACATCTCTGAAGAGCAGGCTCACTATCACCAAGGACACCTCCAAAAACCAGGTGGTCCTTACAATGACCAACATGGACCCTGTGGACACAGCCACATATTACTGT GCACGCCATACTATACCTTCGATCTTTGACTAC TGGGGCCAGGGAATCCTGGTCACCGTCTCCTCAG Antibody 409_11_2 VL (nt) 691 CAGCCTGTGCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGCAACC AGCAGTGACGTTGGTAATTATAACTAT GTCTCCTGGTACCAACACCACCCAGGCAAAGCCCCCAAACTCATGATTTAT GAGGTCAGT AATCGGCCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACGAGGCTGATTATTATTGC AGCTCATATACAAGCAGCAGTCTACTA TTCGGCGGAGGGACCAAGCTGACCGTCCTAG Antibody 409_11_3_v1 VH 692 EVQLVQSGAAVKKTGASVKVSCKAS EYIFTEYY IHWVRQAPGQGLEWMGW INPNSGRT HYAQKFQGRVTMTRDTSITTAYMELSSLRSDDTAVYYC ACLAGEWGYCSTTSCKRGIDGMDV WGQGTTVTVSS Antibody 409_11_3_v1 CDRH1 693 EYIFTEYY Antibody 409_11_3_v1 CDRH2 694 INPNSGRT Antibody 409_11_3_v1 CDRH3 695 ACLAGEWGYCSTTSCKRGIDGMDV Antibody 409_11_3_v1 VL 696 EIVLTQSPLSLPVTPGEPASISCRSS QSLLHSNGYNY LNWYLQKPGQSPQLLIY LGS NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTMYT FGQGTKLEIR Antibody 409_11_3_v1 CDRL1 697 QSLLHSNGYNY Antibody 409_11_3_v1 CDRL2 698 LGS Antibody 409_11_3_v1 CDRL3 699 MQALQTMYT Antibody 409_11_3_v1 VH (nt) 700 GAGGTGCAACTGGTGCAGTCTGGGGCTGCGGTGAAGAAGACTGGGGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GAATACATCTTCACCGAATACTAT ATACACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG ATCAACCCTAACAGTGGTCGCACA CACTATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCACCACAGCCTACATGGAGCTGAGTAGCCTGAGATCTGACGACACGGCCGTGTATTACTGT GCGTGCCTTGCGGGTGAGTGGGGATATTGTAGTACGACCAGCTGCAAAAGAGGGATTGACGGTATGGACGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA Antibody 409_11_3_v1 VL (nt) 701 GAAATTGTGTTGACGCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCATCTCCTGCAGGTCTAGT CAGAGCCTCCTGCATAGTAATGGATACAACTAT TTGAATTGGTACCTGCAGAAGCCAGGGCAGTCTCCACAACTCCTGATCTAT TTGGGTTCT AATCGGGCCTCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAGTGGAGGCTGAGGATGTTGGGGTTTATTACTGC ATGCAAGCTCTACAAACTATGTACACT TTTGGCCAGGGGACCAAGCTGGAGATCAGAC S2D106-v1 mAb VH (nt-CO) 702 GAAGTGCAACTAGTGCAAAGTGGTGCAGAAGTGAAGAAGCCTGGCTCTTCTGTGAAAGTGTCTTGCAAGGCCTCTGGCGGCCCATTTTCCAGCTCTGCCATCTCCTGGGTCAGACAGGCTCCCGGCCAAGGACTGGAGTGGATGGGCGGAATCATCCCTATGGTGGGCACCGCCAACTACGCCCAGAAGTTCCAGGGCAGAGTGACCATCACCGCTGATGAGTCCACCTCTACAGCCTACATGGAACTGTCCTCCCTGAGATCCGAGGACACCGCTGTGTACTACTGTGCTCGGGACTCTCGGTATTGCTCCGGCGGCAGCTGCTACTCCGTGTGGTTCGACCCTTGGGGCCAGGGCACACTGGTGACCGTGTCCAGC Antibody 409_11_1_v2 VH (nt-CO) 703 GAAGTGCAACTAGTGCAAAGTGGTGCAGAAGTCAAGAAGCCAGGCTCCAGCGTTAAAGTGTCTTGCAAGGCCTCTGGCGGACCTTTCTCCTCCAGCGCCATCTCCTGGGTGCGGCAGGCTCCTGGCCAAGGCCTGGAGTGGATGGGCGGCATCATCCCCATCGTGGGCACCGCCAACTACGCCCAGAAGTTCCAGGGCAGAGTGACCATCACAGCCGACGAGTCTACCTCCACCGCTTATATGGAACTGTCTTCTCTGCGGTCCGAGGACACCGCTGTGTACTACTGTGCTAGAGATTCTAGATACTGCTCCGGCGGCAGCTGCTACTCCGTGTGGTTTGACCCTTGGGGCCAGGGAACCCTGGTGACAGTGTCCTCT Antibody 409_11_1_v3 VH (nt-CO) 704 GAAGTGCAACTAGTGCAAAGTGGTGCAGAAGTCAAGAAGCCTGGATCTTCTGTGAAAGTGTCCTGCAAGGCCTCTGGCGGACCATTTAGCTCCTCTGCCATCTCCTGGGTGCGGCAGGCTCCTGGCCAAGGCCTGGAGTGGATGGGCGGCATCATCCCCATGGTGGGCACCGCCAACTACGCCCAGAAGTTCCAGGGCAGAGTGACCATCACCGCTGACGAGTCCACCTCCACAGCCTACATGGAACTGTCCAGCCTGAGATCCGAGGACACCGCTGTGTACTACTGTGCTAGAGATTCTCGGTATTGCTCCGGCGGCTCTTGCTACTCCGTGTTCTTCGACCCTTGGGGCCAGGGCACCCTGGTGACCGTGTCTAGC Antibody 409_11_1_v4 VH (nt-CO) 705 GAAGTGCAACTAGTGCAAAGTGGTGCAGAAGTCAAGAAGCCTGGCTCCTCTGTGAAAGTGTCCTGCAAGGCCTCTGGCGGCCCATTTAGCAGCTCTGCCATCTCCTGGGTGCGGCAGGCTCCTGGACAAGGCCTGGAGTGGATGGGCGGCATCATCCCCATCGTGGGCACAGCTAACTACGCCCAGAAGTTCCAGGGCAGAGTGACCATCACCGCCGACGAGTCCACATCTACCGCCTACATGGAACTGTCCTCCCTGAGATCCGAGGACACCGCTGTGTACTACTGTGCTAGAGATTCTCGGTATTGCTCCGGCGGATCTTGCTACTCCGTGTTCTTCGACCCTTGGGGCCAGGGCACCCTGGTGACCGTGTCTAGC Antibody 409_11_2_v1 VH (nt - CO) 706 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACCCAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACCACCTCTGGAGTCGGCGTGGGCTGGATCCGGCAGCCTCCAGGCAAGGCCCTGGAGTACCTGGCTCTGATCTACTGGGACGACGATAAACGGTATAGCACTAGCCTGAAGTCCAGACTGACAATCACCAAGGATACATCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGACACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCTCT Antibody 409_11_2_v2 VH (nt - CO) 707 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAGCCTACCCAGACCCTGACACTGACCTGTACTTTTTCTGGCTTCTCCGTGACCACCTCCGGCGTGGGAGTGGGCTGGATCAGACAGCCTCCAGGCAAGGCCCTCGAGTACCTGGCTCTGATCTACTTCGATGATGACAAGCGGTATAGCACCTCTCTGAAATCTCGGCTGACAATCACCAAGGACACATCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGACACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v3 VH (nt - CO) 708 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACCCAGACCCTGACACTGACCTGTACTTTTAGCGGCTTCTCCGTGACCACCTCTGGAGTCGGCGTGGGCTGGATCCGGCAGCCTCCTGGCAAAGCTCTGGAGTACCTGGCCCTGATCTACTACGACGATGACAAGCGGTATAGCACATCTCTGAAGTCCAGACTGACCATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCAGTGGATACAGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCTCT Antibody 409_11_2_v4 VH (nt - CO) 709 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAACCAACACAGACCCTGACACTGACCTGTACTTTTAGCGGCTTCTCCGTGACCACCTCTGGCGTGGGAGTGGGCTGGATCAGACAGCCTCCTGGCAAGGCCCTGGAATATCTCGCTCTGATCTACTGGGAGGACGACAAGCGGTACTCCACCAGCCTGAAGTCTCGGCTGACCATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGATACAGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCTCT Antibody 409_11_2_v5 VH (nt - CO) 710 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAGCCTACACAGACCCTGACACTGACCTGTACTTTTTCTGGCTTCTCCGTGACCACCAGCGGCGTGGGCGTGGGCTGGATCCGGCAGCCTCCAGGAAAAGCTCTCGAGTACCTGGCCCTGATCTACTGGAACGACGACAAGCGGTACTCCACCTCTCTGAAGTCCAGACTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCAGCATCTTCGACTATTGGGGCCAGGGCATCCTGGTCACCGTGTCCTCT Antibody 409_11_2_v6 VH (nt - CO) 711 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACCCAGACCCTGACACTGACCTGTACTTTTAGCGGCTTCTCCGTGACCACATCTGGCGTGGGAGTGGGCTGGATCAGACAGCCTCCAGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTGGGACGAGGACAAGCGGTATTCCACCTCTCTGAAATCTCGGCTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v7 VH (nt - CO) 712 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAACCAACCCAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACCACCAGCGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTCGAGTACCTGGCTCTGATCTACTGGGACAACGACAAGCGGTATAGCACTTCTCTGAAGTCCAGACTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGATACAGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCTCT Antibody 409_11_2_v8 VH (nt - CO) 713 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACACAGACCCTGACACTGACCTGTACTTTTTCTGGCTTCTCCGTGACCACCAGCGGCGTGGGAGTGGGCTGGATCAGACAGCCTCCAGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTTCGAGGACGACAAGCGGTATTCCACCTCTCTGAAATCTCGGCTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v9 VH (nt - CO) 714 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAACCAACCCAGACCCTGACACTGACCTGTACCTTCTCCGGCTTTTCTGTGACCACCTCTGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTCGAGTACCTGGCTCTGATCTACTTCAACGACGACAAGCGGTATAGCACTAGCCTGAAGTCCAGACTGACAATCACCAAGGATACATCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGACACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCTCT Antibody 409_11_2_v10 VH (nt - CO) 715 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAGCCTACCCAGACCCTGACACTCACATGTACCTTTTCTGGCTTCTCCGTGACCACTAGCGGCGTGGGAGTGGGCTGGATCCGGCAACCACCTGGCAAAGCTCTGGAATACCTGGCCCTGATCTACTACGAGGACGACAAGCGGTATTCTACCTCTCTGAAGTCCAGACTGACCATCACCAAGGATACATCCAAGAACCAGGTGGTGCTGACCATGACCAACATGGATCCTGTGGACACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v11 VH (nt - CO) 716 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAGCCTACCCAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACCACATCTGGAGTGGGCGTGGGCTGGATCAGACAGCCTCCAGGCAAGGCCCTCGAGTACCTGGCTCTGATCTACTACAACGACGACAAGCGGTATTCCACCTCTCTGAAAAGCCGGCTGACTATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGATACAGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v12 VH (nt - CO) 717 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAACCAACCCAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACAACTAGCGGAGTCGGCGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTTCGATGAGGACAAGCGGTATAGCACCTCTCTGAAGTCCAGACTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCTCT Antibody 409_11_2_v13 VH (nt - CO) 718 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACCCAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACCACCAGCGGCGTCGGCGTGGGCTGGATCCGGCAGCCTCCAGGAAAAGCTCTGGAGTACCTGGCCCTGATCTACTTCGACAACGACAAGCGGTATTCTACTTCTCTGAAGTCCAGACTGACCATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACAATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCAGC Antibody 409_11_2_v14 VH (nt - CO) 719 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACCCAGACCCTGACACTGACATGTACTTTTTCTGGCTTCTCCGTGACCACCAGCGGAGTCGGCGTGGGCTGGATCAGACAGCCTCCAGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTACGACGAGGACAAGCGGTATTCCACCTCTCTGAAATCTCGGCTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCAGC Antibody 409_11_2_v15 VH (nt - CO) 720 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAGCCCACACAGACCCTGACACTGACCTGCACCTTTTCTGGCTTCTCCGTGACCACCTCCGGCGTGGGAGTGGGCTGGATCAGACAGCCTCCAGGCAAAGCTCTCGAGTACCTGGCCCTGATCTACTACGACAACGACAAGCGGTACTCCACCTCTCTGAAGTCTCGGCTGACTATCACCAAGGATACAAGCAAGAACCAAGTGGTGCTGACCATGACCAACATGGATCCTGTGGACACCGCTACCTACTATTGTGCCAGACACACCATCCCTTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v16 VH (nt - CO) 721 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACACAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACCACAAGCGGAGTCGGCGTGGGCTGGATCCGGCAGCCTCCAGGCAAAGCTCTGGAATACCTGGCCCTGATCTACTGGGAGGAGGACAAGCGGTATTCCACCTCTCTGAAGTCCAGACTGACTATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCTATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCAGC Antibody 409_11_2_v17 VH (nt - CO) 722 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAACCAACCCAGACCCTGACACTGACCTGTACCTTTAGCGGCTTCTCCGTGACCACCTCTGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTGGGAGAACGACAAGCGGTATAGCACATCTCTGAAGTCCAGACTGACAATCACCAAGGACACTTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCTCT Antibody 409_11_2_v18 VH (nt - CO) 723 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTCAAACCAACTCAGACCCTGACACTGACCTGTACCTTTTCCGGCTTCTCCGTGACCACATCTGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTGGAACGAGGACAAGCGGTATAGCACCTCTCTGAAGTCCAGACTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCTATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCAGC Antibody 409_11_2_v19 VH (nt - CO) 724 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAGCCTACCCAGACCCTGACACTGACCTGTACTTTTTCTGGCTTCTCCGTGACCACCTCTGGAGTGGGCGTGGGCTGGATCCGGCAGCCTCCAGGCAAGGCCCTCGAGTACCTGGCTCTGATCTACTGGAACAACGACAAGCGGTATAGCACATCTCTGAAGTCCAGACTGACAATCACCAAAGATACCTCCAAGAATCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGACACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v20 VH (nt - CO) 725 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAACCAACCCAGACCCTGACACTGACCTGTACTTTTTCTGGCTTCTCCGTGACCACAAGCGGAGTGGGCGTGGGCTGGATCAGACAGCCTCCTGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTTCGAGGAGGACAAGCGGTATTCCACCTCTCTGAAGTCTCGGCTCACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v21 VH (nt - CO) 726 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACCCAGACCCTGACACTGACCTGTACCTTTAGCGGCTTCTCCGTGACTACATCTGGCGTGGGAGTCGGCTGGATCCGGCAGCCTCCAGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTTCGAGAACGACAAGCGGTATAGCACCTCTCTGAAGTCCAGACTGACAATCACCAAAGATACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGACACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCTCT Antibody 409_11_2_v22 VH (nt - CO) 727 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAACCAACCCAGACCCTGACACTGACCTGTACCTTCTCCGGCTTTTCTGTGACCACATCTGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTTCAACGAGGACAAGCGGTATAGCACCTCTCTGAAGTCCAGACTGACAATCACCAAGGACACCTCCAAGAACCAAGTG GTGCTGACCATGACCAACATGGACCCTGTGGATACTGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v23 VH (nt - CO) 728 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAACCAACCCAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACTACCTCTGGAGTCGGCGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTGGAGTACCTGGCTCTGATCTACTTCAACAACGACAAGCGGTATAGCACATCTCTGAAGTCCAGACTGACAATCACCAAGGACACCTCCAAGAATCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCAGC Antibody 409_11_2_v24 VH (nt - CO) 729 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAACCAACCCAGACCCTGACACTCACATGTACTTTTTCTGGCTTCTCCGTGACCACAAGCGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTACGAGGAGGACAAGCGGTATTCTACCTCTCTGAAGTCCAGACTGACCATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v25 VH (nt - CO) 730 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTCAAACCAACCCAGACCCTGACACTGACCTGTACCTTCTCCGGCTTTTCTGTGACTACATCTGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCTGGCAAGGCCCTGGAATACCTGGCTCTGATCTACTACGAGAACGACAAGCGGTATTCCACCTCTCTGAAGTCCAGACTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCAGCATCTTCGACTACTGGGGCCAGGGCATCCTGGTGACCGTGTCCAGC Antibody 409_11_2_v26 VH (nt - CO) 731 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTCGTGAAGCCTACCCAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACTACAAGCGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCAGGCAAAGCTCTGGAATACCTGGCCCTGATCTACTACAACGAGGACAAGCGGTATTCTACCTCTCTGAAGTCCAGACTGACAATCACCAAGGACACCTCCAAGAACCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGATACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody 409_11_2_v27 VH (nt - CO) 732 CAAATCACTCTAAAGGAAAGTGGTCCAACTCTGGTGAAGCCTACCCAGACCCTGACACTGACCTGTACCTTTTCTGGCTTCTCCGTGACCACCTCTGGCGTGGGAGTGGGCTGGATCCGGCAGCCTCCAGGCAAGGCCCTCGAGTACCTGGCTCTGATCTACTACAACAACGACAAGCGGTATTCTACTAGCCTGAAGTCCAGACTGACAATCACCAAGGATACATCCAAAAATCAAGTGGTGCTGACCATGACCAACATGGACCCTGTGGACACCGCTACCTACTACTGCGCCAGACACACCATCCCCTCCATCTTCGACTACTGGGGCCAGGGCATCCTGGTCACCGTGTCCAGC Antibody S2D106-v1.1 VH (nt) 733 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTTTCCTGCAAGGCTTCT GGAGGCCCCTTCAGCAGCTCTGCT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGG ATCATCCCTATGGTAGGTACAGCA AACTATGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGT GCGAGAGATTCGCGCTATTGTAGTGGTGGTAGCTGCTACTCCGTCTGGTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA Antibody 409_11_1_v2 VH (nt) 734 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTTTCCTGCAAGGCTTCT GGAGGCCCCTTCAGCAGCTCTGCT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGG ATCATCCCTATAGTAGGTACAGCA AACTATGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGT GCGAGAGATTCGCGCTATTGTAGTGGTGGTAGCTGCTACTCCGTC TGG TTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA Antibody 409_11_1_v3 VH (nt) 735 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTTTCCTGCAAGGCTTCT GGAGGCCCCTTCAGCAGCTCTGCT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGG ATCATCCCTATGGTAGGTACAGCA AACTATGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGT GCGAGAGATTCGCGCTATTGTAGTGGTGGTAGCTGCTACTCCGTCTTCTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA Antibody 409_11_1_v4 VH (nt) 736 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTTTCCTGCAAGGCTTCT GGAGGCCCCTTCAGCAGCTCTGCT ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGG ATCATCCCTATAGTAGGTACAGCA AACTATGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGT GCGAGAGATTCGCGCTATTGTAGTGGTGGTAGCTGCTACTCCGTCTTCTTCGACCCC TGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA Antibody S2E12-v1.1 VL (nt) 737 GATATTGTGTTGACGCAGACTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGT CAGAGTGTTAGCAGCAGTTAC TTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTAT GGTGCATCC AGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGT CAGCAGTATGTTGGCTTAACAGGGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAA Antibody 409_11_4_v2 VL (aa) 738 DIVLTQTPGTLSLSPGERATLSCRAS QSVSSSY LAWYQQKPGQAPRALIY GAS SRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYVGLTGWTFGQGTKVEIK Antibody 409_11_4_v2 VL (nt) 739 GATATTGTGTTGACGCAGACTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGGGCCAGT CAGAGTGTTAGCAGCAGTTAC TTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGG GCC CTCATCTAT GGTGCATCC AGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCAGTGTATTACTGT CAGCAGTATGTTGGCTTAACAGGGTGGACG TTCGGCCAAGGGACCAAGGTGGAAATCAAA Antibody 409_3_1_v2 VH (aa) 740 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGW INPNSGGT NFAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYC ASSGYLGYYYYGMDV WGQGTTVTVSS Antibody 409_3_1_v3 VH (aa) 741 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGW INPNSGGT NFAQKFQGRVTMTRDTSISTAYMELSSLRSDDTAVYYC ASSGYLGYYYYGMDV WGQGTTVTVSS Antibody 409_3_1_v4 VH (aa) 742 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGW INPNSGGT NFAQKFQGRVTMTRATSISTAYMELSRLRSDDTAVYYC ASSGYLGYYYYGMDVWGQGTTVTVSS Antibody 409_3_1_v5 VH (aa) 743 EVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYY IHWVRQAPGQGLEWMGW INPNSGGT NFAQKFQGRVTMTRDTSFSTAYMELSRLRSDDTAVYYC ASSGYLGYYYYGMDVWGQGTTVTVSS Antibody 409_11_4_v3 VL (aa) 744 DIVLTQTPGTLSLSPGERATLSCRAS QSVS SSY LAWYQQKPGQAPRLLIY GAS SRATGIP DRFSGSGSGTDFTLTISRLEPEDFAVYYC Q QYVGLTGFT FGQGTKVEIK Antibody 409_11_4_v3 CDRL3 (aa) 745 QQYVGLTGFT Antibody 409_11_4_v4 VL (aa) 746 DIVLTQTPGTLSLSPGERATLSCRAS QSVS SSY LAWYQQKPGQAPRLLIY GAS SRATGIP DRFSGSGSGTDFTLTISRLEPEDFAVYYC Q QYVGLTGYT FGQGTKVEIK Antibody 409_11_4_v4 CDRL3 (aa) 747 QQYVGLTGYT Antibody 409_11_4_v5 VH (aa) 748 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGF IVVGSGNT NYAQKFHERVTITRDMS TSTAYMELSSLRSEDTAVYYCAS PY CSGGSCSDGFDI WGQGTMVTVSS Antibody 409_11_4_v6 VH (aa) 749 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGY IVVGSGNT NYAQKFHERVTITRDMS TSTAYMELSSLRSEDTAVYYCAS PY CSGGSCSDGFDI WGQGTMVTVSS Antibody 409_11_4_v7 VH (aa) 750 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGW IVVGSGNT NYAQKFH ERVTITRDMS TSTAYMELSSLRSEDTAVYYCAS PY CSGGSCSDAFDI WGQGTMVTVSS Antibody 409_11_4_v7 CDRH3 and N-terminal Ala-Ser (aa) 751 ASPYCSGGSCSDAFDI Antibody 409_11_4_v8 VH (aa) 752 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGW IVVGSGNT NYAQKFHERVTITRDMS TSTAYMELSSLRSEDTAVYYCAS PY SSGGSSSDGFDI WGQGTMVTVSS Antibody 409_11_4_v8 CDRH3 and N-terminal Ala-Ser (aa) 753 ASPYSSGGSSSDGFDI Antibody 409_11_4_v9 VH (aa) 754 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFT SSA VQWVRQARGQRLEWVGW IVVGSGNT NYAQKFHERVTITRDMS TSTAYMELSSLRSEDTAVYYCAS PY PSGGSPSDGFDI WGQGTMVTVSS Antibody 409_11_4_v9 CDRH3 and N-terminal Ala-Ser (aa) 755 ASPYPSGGSPSDGFDI Antibody 409_11_4_v10 VH (aa) 756 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGW IVVGSGNT NYAQKFHERVTITRDMSTSTA MELSSLRSEDTAVYYCAS PY ASGGSASDGFDI WGQGTMVTVSS Antibody 409_11_4_v10 CDRH3 and N-terminal Ala-Ser (aa) 757 ASPYASGGSASDGFDI Antibody 409_11_4_v11 VH (aa) 758 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGF IVVGSGNT NYAQKFH ERVTITRDMS TSTAYMELSSLRSEDTAVYYCAS PY CSGGSCSEGFDI WGQGTMVTVSS Antibody 409_11_4_v12 VH (aa) 759 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGW IVVGSGNT NYAQKFHERVTITRDMS TSTAYMELSSLRSEDTAVYYCAS PY CSGGSCSEGFDI WGQGTMVTVSS Antibody 409_11_4_v12 CDRH3 with N-terminal Ala-Ser (aa) 760 ASPYCSGGSCSEGFDI Antibody 409_11_4_v13 VH (aa) 761 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGA IVVGSGNT NYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCAS PYCSGGSCSDGFDIWGQGTMVTVSS Antibody 409_11_1_v5 VH (aa) 762 EVQLVQSGAEVKKPGSSVKVSCKASGGPFSSSA ISWVRQAPGQGLEWMGG IIPMVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYC ARDSRYASGGSAYSVWFDPWGQGTLVTVSS Antibody 409_11_1_v5 CDRH3 (aa) 763 ARDSRYASGGSAYSVWFDP Antibody 409_11_1_v6 VH (aa) 764 EVQLVQSGAEVKKPGSSVKVSCKASGGPFSSSA ISWVRQAPGQGLEWMGG IIPMVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYC ARDSRYSSGGSSYSVWFDPWGQGTLVTVSS Antibody 409_11_1_v6 CDRH3 (aa) 765 ARDSRYSSGGSSYSVWFDP SARS-CoV-2 S2E12-v1 mAb CDRH3 (IMGT) (aa) 766 PYCSGGSCSDGFDI SARS-CoV-2 S2E12-v1 heavy chain (MLNS) 767 QVQLVQSGPEVKKPGTSVRVSCKAS GFTFTSSA VQWVRQARGQRLEWVGW IVVGSGNT NYAQKFHERVTITRDMSTSTAYMELSSLRSEDTAVYYCAS PYCSGGSCSDGFDI WGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK SARS-CoV-2 409_11_4_v2 VL light chain 768 DIVLTQTPGTLSLSPGERATLSCRAS QSVSSSY LAWYQQKPGQAPRALIY GAS SRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYVGLTGWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC SARS-CoV-2 409_11_4_v7 CDRH3 (IMGT) (aa) 769 PYCSGGSCSDAFDI SARS-CoV-2 409_11_4_v8 CDRH3 (IMGT) (aa) 770 PYSSGGSSSDGFDI SARS-CoV-2 409_11_4_v9 CDRH3 (IMGT) (aa) 771 PYPSGGSPSDGFDI SARS-CoV-2 409_11_4_v10 CDRH3 (IMGT) (aa) 772 PYASGGSASDGFDI SARS-CoV-2 409_11_4_v11 and 409_11_4_v12 CDRH3 (IMGT) (aa) 773 PYCSGGSCSEGFDI example Example 1 Human antibodies bind to SARS -CoV -2 spike protein

Monoclonal antibodies isolated from human patients recovered from SARS-CoV-2 infection. Briefly, EBV-immortalized memory B cells were classified based on the intact ectodomain of the SARS-CoV-2 spike protein bound to the trimeric prefusion conformation. A biotin moiety was attached to the C-terminus of the spike protein, and the spike protein was biotin-labeled, coupled to fluorescent streptavidin (AF647 fluorophore), and used to stain B cells, which were then sorted based on fluorescence in order to bind to the trimeric prefusion spike protein. The monoclonal antibodies identified by this method were recombinantly expressed in ExpiCHO cells transiently co-transfected with plastids expressing the heavy and light chains. Example 2 Binding of antibodies to SARS - CoV -1 RBD and SARS - CoV -2 RBD

Binding of monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection to the RBD of SARS-CoV-1 and SARS-CoV-2 spike proteins was assessed using an enzyme-linked immunosorbent assay (ELISA).

Briefly, 96-well plates were prepared with SARS-CoV-2 RBD (in-house produced; residues 331-550 of the spike protein of βCoV/Wuhan-Hu-1/2019, accession number MN908947) or SARS-CoV (in this paper Also described as SARS-CoV-1) RBD (Sino Biological) coating. Wells were washed and blocked with PBS + 1% BSA for 1 hour at room temperature and then incubated with serial dilutions of recombinant monoclonal antibody for 1 hour at room temperature. Bound antibody was detected by incubating alkaline phosphatase-conjugated goat anti-human IgG (Southern Biotechnology: 2040-04) for 1 hr at room temperature, and by incubation with 1 mg/ml p-nitrophenyl phosphate. Development was performed in 0.1 M glycine buffer (pH 10.4) at room temperature for 30 minutes. Optical density (OD) values were measured at a wavelength of 405 nm in an ELISA reader (Powerwave 340/96 spectrophotometer, BioTek).

The results of the ELISA analysis are shown in Figures 1A-1D. In each panel, binding to the RBD of SARS-CoV-2 is shown in the upper panel, and binding to the RBD of SARS-CoV-1 is shown in the lower panel. Calculated EC50 values (in ng/ml) are shown in the box on the right side of the figure and in Table 3. Table 3. Binding of antibodies to SARS RBD (ELISA ) (EC50ng / ml ) Antibody EC50 : SARS-CoV-2 RBD EC50 : SARS-CoV-1 RBD S2X11 18.70 - S2X14 26.57 - S2X16 17.02 - S2X19 19.44 - S2X21 20.38 - S2X25 25.69 - S2X28 - - S2X30 37.94 - S2X33 34.01 - S2X35 48.26 84.64 S2X41 20.01 - S2X42 23.45 26.08 S2X47 92.02 - S2X52 14.18 - S2X55 13.75 - S2X56 12.73 - S2X58 22.91 - S2X59 12.56 - S2X67 17.91 - S2X71 11.53 - S2X73 12.03 - S2X76 11.73 - S2X78 14.34 -

Other assays using the same procedure were performed using other antibodies. The results are shown in Figures 8A and 8B. In each of these figures, binding to the SARS-CoV-2 RBD is shown in the left panel, and binding to the SARS-CoV-1 RBD is shown in the right panel. Calculated EC50 values (in ng/ml) are shown in the boxes to the right of each figure.

The same procedure was performed with other antibodies. The results are shown in Figures 10A-10E. In each of these figures, binding to the SARS-CoV-2 RBD is shown in the upper figure, and binding to the SARS-CoV-1 SARS RBD is shown in the lower figure. Calculated EC50 values (in ng/ml) are shown in the box to the right of each figure when available. In this assay, antibody S2E12 (VH amino acid sequence of SEQ ID NO.: 399; VL amino acid sequence of SEQ ID NO.: 403) bound SARS-CoV-2 RBD with an EC50 of 43.40 ng/ml.

Similar methods were used to determine the binding of additional antibodies to the SARS-CoV-2 RBD. The results are shown in Figures 22A and 22B. Calculated EC50 values are shown in the boxes to the right of each figure. Example 3 Binding of Antibodies to SARS - CoV -1 and SARS - CoV -2 Spike Proteins and to SARS - CoV -1 and SARS - CoV -2 RBDs

Assessment of certain human monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection with the spike protein of SARS-CoV-2 and with RBD and SARS-CoV-1 by enzyme-linked immunosorbent assay (ELISA) Binding of the SARS-CoV-2 spike protein.

Briefly, 96-well plates were prepared with SARS-CoV spike protein S1 subunit protein (Sino Biological), SARS-CoV-2 RBD (in-house generated; residue 331 of the spike protein of βCoV/Wuhan-Hu-1/2019). -550, Accession No. MN908947) or SARS-CoV RBD (Sino Biological) coating. Wells were washed and blocked with PBS + 1% BSA for 1 hour at room temperature and then incubated with serial dilutions of recombinant monoclonal antibody for 1 hour at room temperature. Bound antibody was detected by incubating alkaline phosphatase-conjugated goat anti-human IgG (Southern Biotechnology: 2040-04) for 1 hr at room temperature, and by incubation with 1 mg/ml p-nitrophenyl phosphate. Development was performed in 0.1 M glycine buffer (pH 10.4) at room temperature for 30 minutes. Optical density (OD) values were measured at a wavelength of 405 nm in an ELISA reader (Powerwave 340/96 spectrophotometer, BioTek).

ELISA analysis results are shown in Figures 4A-4N. Calculated EC50 values (in ng/ml) are shown in the boxes to the right of each figure.

Similar methods were used to assess the binding of additional monoclonal antibodies to the SARS-CoV-1 and SARS-CoV-2 spike proteins and to the SARS-CoV-1 and SARS-CoV-2 spike proteins RBD. The results are shown in Figures 18A-18E. Calculated EC50 values (ng/ml) are shown in the boxes to the right of each figure.

Binding of additional monoclonal antibodies to the SARS-CoV-1 spike, the SARS-CoV-1 spike RBD, and the SARS-CoV-2 spike RBD was determined by a similar method. The results are shown in Figures 20A, 20B, 21A and 21B. The boxes to the right of the figures show the calculated EC50 values (ng/ml). Example 4 Antibodies competitively bind to human ACE2 for RBD binding

Competitive binding of recombinant monoclonal antibodies and human ACE2 to RBD was measured by competition ELISA. Recombinant antibody systems were generated using monoclonal antibodies isolated from patients who had recovered from SARS-CoV-2 infection.

Briefly, ELISA plates were coated with recombinant human ACE2 (generated in-house). Coating was performed with ACE2 at 2 ug/ml in PBS. The plates were incubated overnight at 4°C and blocked with the blocking agent casein (1% casein from Thermofisher) for 1 hour at room temperature. Serial dilutions of monoclonal antibodies were incubated with SARS-CoV-2 RBD at 20ng/ml (RBD fused to mouse Fc from Sino Biological) for 30 minutes at 37°C and then transferred to ACE2-coated on a plate and re-incubated at room temperature. Plates were washed and binding of RBD to ACE2 was detected using a polyclonal goat anti-mouse Fc-AP antibody (Southern Biotech). After additional washing, AP substrate pNPP (Sigma) was added and the disc was incubated at room temperature for 20 minutes before measuring the amount of adsorption at 405 nm using a spectrophotometer (Powerwave 340 Biotek). The results are shown in FIG. 2 .

Further analysis was performed using methods similar to other monoclonal antibodies. The results are shown in Figures 13A, 13B, 23A and 23B. In these figures, the calculated IC50 values are shown to the right of each figure. Example 5 Neutralization of SARS- CoV -2 pseudopatterned MLV by recombinant human monoclonal antibodies

Monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested against SARS-CoV-2 pseudo-patterned virus in neutralization assays.

Briefly, murine leukemia virus (MLV) pseudopatterned with the SARS-CoV-2 spike protein (SARS-CoV-2pp) was used. VeroE6 cell line was used as target cells and was seeded one day before virus and antibody addition. SARS-CoV-2pp was activated with trypsin TPCK at 10ug/ml. Activated SARS-CoV-2pp was added to serial dilutions of antibodies and incubated for 48 hours. The initial concentration of antibody was 5ug/ml per antibody, 3-fold dilution. Luminescence was measured after aspiration of cell culture supernatant and addition of Bio-Glo substrate (Promega).

The results are shown in Figures 3A-3F. Calculated EC50 values (in ng/ml) are shown on the right side of each of these figures. Table 4 shows the calculated IC50, IC80 and IC90 values in ng/ml. Table 4. Neutralization against MLV pseudopatterned with SARS - CoV - 2 S protein ng/ml Antibody IC50 IC80 IC90 S2X47 3 12 25 S2X16 6 twenty two 46 S2X56 8 38 94 S2X55 11 31 57 S2X30 15 31 46 S2X58 19 40 62 S2X76 11 37 74 S2X71 12 48 109 S2X11 28 64 103 S2X28* 13 573 5185 S2X19 twenty two 80 169 S2X14 39 127 255 S2X52 37 134 284 S2X41 41 140 285 S2X78 29 122 285 S2X21 42 138 279 S2X35 92 320 661 S2X33 35 412 1734 S2X25 79 532 1624 S2X73 41 229 628 S2X59 52 234 563 S2X67 45 225 573 S2X42 -- -- --

Additional monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested against SARS-CoV-2 pseudo-patterned virus in neutralization assays using the same procedure. The results are shown in Figures 5A-5D and Figures 7A-7D. The antibody labeled "S2H58" in Figure 7D comprises the VH amino acid sequence set forth in SEQ ID NO.:228 and the VL amino acid sequence set forth in SEQ ID NO.:238. Calculated EC50 values for the antibodies in Figures 5A-5D are shown in the boxes to the right of each figure. Calculated EC50 and EC90 values for the antibodies in Figures 7A-7D are shown in Table 5. Table 5. Neutralization against MLV pseudopatterned with SARS - CoV - 2 S protein Antibody EC50 (ng/ml) EC90 (ng/ml) SN12 37.22 79.099 S2N19 98.71 516.291 S2N22 36.19 58.835 S2N24 65.53 167.841 S2N25 39.22 88.528 S2N27 55.97 129.421 S2N28 32.72 174.533 S2N41 0.1125 - S2X11 50.77 245.392 S2X71 19.09 174.137 S2X76 33.19 67.599 S2H58 9.653 54.544 S2H67 60.12 221.856 S309 727.2 1472.870

Additional monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested against SARS-CoV-2 pseudo-patterned virus in neutralization assays using the same procedure. The results are shown in Figures 9A-9F. The calculated IC50, IC80 and IC90 values are shown below the graph in each figure. Antibody S2E12 shown in Figure 9E comprises the VH amino acid sequence of SEQ ID NO.:399 (CDRH1-H3 of SEQ ID NO.:400, 401 and 766, respectively) and the VL amino acid sequence of SEQ ID NO.:403 Sequences (CDRL1-CDRL3 of SEQ ID NO.: 404-406, respectively).

Neutralization of infection by other antibodies was analyzed using a similar method. The results are shown in Figures 11A-11D. Calculated IC50, IC80 and IC90 values are shown to the right of each figure.

Other antibodies were tested in neutralization assays against SARS-CoV-2 pseudo-patterned virus using similar methods. The results are shown in Figures 17A-17C. Calculated IC50, IC80 and IC90 values are shown below each figure.

Other antibodies were tested in neutralization assays against SARS-CoV-2 pseudo-patterned virus using similar methods. The results are shown in Figures 19A-19E. The calculated IC50, IC80 and IC90 values are shown to the right of the graph in each figure. Example 6 Antibody Neutralization of Live SARS - CoV -2

Monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested against live SARS-CoV-2 virus in neutralization assays.

Briefly, Vero E6 cells cultured in DMEM supplemented with 10% FBS (VWR) and 1x penicillin/streptomycin (Thermo Fisher Scientific) were seeded at 20,000 cells/well in white 96-well dishes and attached. overnight. Serial 1:4 dilutions of monoclonal antibodies were combined with 200 pfu of SARS-CoV-2 (isolate USA-WA1/2020, passage 3, passage 3, in Vero E6 cells at 37°C in a BSL-3 facility ) together for 30 minutes. The cell supernatant was removed and the virus-antibody mixture was added to the cells. 24 hours post-infection, cells were fixed with 4% paraformaldehyde for 30 minutes, followed by two PBS (pH 7.4) washes, and permeabilized with 0.25% Triton X-100 in PBS for 30 minutes. After blocking in 5% milk powder/PBS for 30 minutes, cells were incubated with a primary antibody targeting SARS-CoV-2 nucleocapsid protein (Sino Biological, cat. 40143-R001) at a 1:2000 dilution for 1 hour . After washing and incubation for 1 hour with secondary Alexa647-labeled antibody mixed with 1 µg/ml Hoechst33342, the discs were imaged on an automated cell imaging reader (Cytation 5, Biotek) using the software provided by the manufacturer Nucleocapsid-positive cells were counted. Data were processed using Prism software (GraphPad Prism 8.0).

The results are shown in Figures 6A and 6B and Tables 6 and 7 (EC50 and EC90 values, ng/ml). The calculated IC50 values (ng/ml) are shown in Table 8. Table 6. X (interpolated) S309-v2 LS (incoming) S2X71 (incoming) S2X30 (incoming) S2X56 (incoming) S2X76 (incoming) S2X16 (incoming) S2X35 (incoming) S2X28 (incoming) S2X55 (incoming) S2X11 (incoming) 287.351 90.000 81.753 50.000 37.711 90.000 7.417 50.000 24.483 90.000 6.720 50.000 72.423 90.000 15.551 50.000 18.972 90.000 5.243 50.000 34.097 90.000 7.570 50.000 376.690 90.000 94.413 50.000 53.786 90.000 7.373 50.000 29.826 90.000 11.470 50.000 19.539 90.000 6.693 50.000 Table 7. X (interpolated) S309-v2 LS (incoming) S2X71 (incoming) S2X30 (incoming) S2X56 (incoming) S2X58 (incoming) S2X76 (incoming) S2X16 (incoming) S2X35 (incoming) S2X28 (incoming) S2X55 (incoming) S2X11 (incoming) 452.707 90.000 199.976 50.000 110.659 90.000 24.449 50.000 351.094 90.000 132.514 50.000 364.145 90.000 95.154 50.000 228.754 90.000 58.650 50.000 108.265 90.000 34.773 50.000 156.012 90.000 36.085 50.000 840.691 90.000 243.758 50.000 159.046 90.000 35.974 50.000 101.959 90.000 34.220 50.000 86.467 90.000 23.224 50.000 Table 8. Antibody IC50 Experiment 1 IC90 Experiment 1 IC50 Experiment 2 IC90 Experiment 2 S309-v2 LS 81.75 297 201.8 452 S2X71 7.417 32 24.59 110 S2X30 6.720 twenty four 134.4 351 S2X56 15.49 72 94.92 364 S2X58 - - 58.09 228 S2X76 5.243 19 34.56 108 S2X16 7.512 34 35.55 156 S2X35 94.41 377 237.4 840 S2X28 7.140 54 35.75 159 S2X55 11.44 30 35.48 102 S2X11 6.679 20 22.53 86

Twenty-two other antibodies were tested in neutralization assays against live SARS-CoV-2 virus using similar methods, as well as the comparative antibody S309-v2 (VH set forth in SEQ ID NO.: 342, SEQ ID NO.: 346 VL as set forth in (CDRH1-H3 and L1-L3 as set forth in SEQ ID NO.: 343-345 and 347-349, respectively)). The results are shown in Figures 16A-16D. S2H58-v2 comprises the VH amino acid sequence set forth in SEQ ID NO: 228 and the VL amino acid sequence set forth in SEQ ID NO: 238 (kappa light chain). S2E12 comprises the VH amino acid sequence set forth in SEQ ID NO.:399 (CDRH1-H3 set forth in SEQ ID NO.:400, 401 and 766, respectively) and the VL set forth in SEQ ID NO.:403 Amino acid sequences (CDRL1-L3 set forth in SEQ ID NO.: 404-406, respectively). Calculated IC50 values (ng/ml) are shown in Tables 9-12. Calculated EC50 and EC90 values (ng/ml) are shown in Tables 13-16. Table 9. Antibody IC50 S309-v2 123.8 S2N22 13.58 S2N12 23.68 S2N28 17.59 S2N25 13.64 S2H58-v2 6.337 Table 10. Antibody IC50 S309-v2 145.7 S2E9 24.93 S2E6 13.52 S2E13 about 14.02 S2K4 26.36 S2E14 8.300 S2E7 24.43 S2E12 5.409 Table 11. Antibody IC50 S309-v2 146.0 S2H37 48.67 S2H73 12.72 S2H40 18.63 S2H70 52.69 S2H71 5.580 Table 12. Antibody IC50 S309-v2 173.7 S2X30 11.42 S2H58-v1 8.362 S2H66 633.0 S2H62 24.17 S2H30 28.80 Table 13. Antibody EC50 EC90 S309-v2 126 438 S2N22 13 46 S2N12 25 77 S2N28 18 44 S2N25 13 49 S2H58-v2 6 19 Table 14. Antibody EC50 EC90 S309-v2 145 342 S2E6 16 70 S2E9 25 66 S2E13 14 17 S2K4 13 49 S2E14 9 41 S2E12 5 16 Table 15. Antibody EC50 EC90 S309-v2 (with M428L and N434S Fc mutations) 151 461 S2H37 49 169 S2H73 13 65 S2H40 20 65 S2H70 52 234 S2H71 6 20 Table 16. Antibody EC50 EC90 S309-v2 (with M428L and N434S Fc mutations) 174 588 S2X30 12 34 S2H58 8 twenty three S2H66 584 5000 S2H62 twenty four 82 S2H30 27 121

Neutralization assays were performed using additional monoclonal antibodies using a similar method. The results are shown in Figures 25A and 25B. Figure 25A shows the results for the four antibodies as well as the comparative antibodies S309 N55Q LS and S2X193. The S309 N55Q LS (also referred to herein as S309-v2) comprises the VH sequence set forth in SEQ ID NO:342 and the VL sequence set forth in SEQ ID NO:346, and comprises M428L and N434S mutations in the Fc region. Figure 25B shows the results for antibodies S2X129 and S2X132, and four comparative antibodies. IC50 and interpolated EC50 and EC90 values (ng/ml) are shown in Table 17. Table 17. Antibody IC50 EC50 EC90 S309 N55Q_MLNS (2 measurements) 268.4; 205.4 256;194 635; 634 S2X127 17.18 17 54 S2X129 (2 measurements) 5.379; 4.104 5;4 12; 12 S2X132 (2 measurements) 16.50; 9.265 16;9 38; 24 S2X190 24.18 twenty three 64 S2X193 26.69 26 61 S2X195 17.85 17 47 S2X219 20.63 20 69 S2X246 7.894 8 twenty two

Neutralization by other antibodies (represented as recombinant IgGl with wild-type or M428L/N434S ("LS")-modified Fc) was assessed using the VSV-luc (Spike protein D19) pseudovirus. Curves are shown in Figure 26; IC50 values and interpolated EC50 and EC90 values (ng/ml) are shown in Table 18. Table 18. Antibody IC50 EC50 EC90 S309 (wt) 25.69 25.8 121 S2E12-LS 1.401 1.4 11.9 S2M11-v1-LS 0.9143 1.1 14.4 S2D106-LS 3.376 3.6 15.4 409_11_3_v1-LS 4.085 5.3 40.9 S2X227-v2-LS 4.446 5.3 27.5 409_11_2_v1-LS 2.327 2.4 9.3

These antibodies were also tested for neutralization of live SARS-CoV-2. Curves are shown in Figure 27; data from triplicate wells SARS-CoV-2-luc, MOI 0.1, 6h infection. IC50 and interpolated EC50 and EC90 values (ng/ml) are shown in Table 19. Table 19. Antibody IC50 EC50 EC90 S2E12-LS 4.844 5 30 S2M11-v1-LS 3.214 4 11 S2D106-LS 4.485 6 twenty two 409_11_3_v1-LS 8.233 10 39 S2X227-v2-LS 7.061 10 44 409_11_2_v1-LS 5.073 5 20 S309 84.30 79 289 Example 7 Generation of S2X16 , S2X30 , S2X35 and S2X47 variant antibodies

Recombinant IgGl antibodies were generated using the VH and VL sequences of antibodies S2X16, S2X30, S2X35 and S2X47 or engineered variants thereof. Combinations were generated as indicated in Table 20. Each of the antibodies was produced by transient transfection and expression of plastid vectors encoding recombinant antibodies in HD 293F cells (GenScript). Cells were harvested on day 4 and IgG performance was verified by Western blotting and protein A titer analysis. Table 20. Antibody VH (WT/ variant ) VH amino acid SEQ ID NO. VL (WT/ variant ) VL amino acid SEQ ID NO. S2X16-11 WT twenty two WT 26 S2X16-21 W50F 150 WT 26 S2X16-12 WT twenty two N33Q 154 S2X13-23 W50F 150 G34A 157 S2X30-11 WT 42 WT 46 S2X30-21 D112E 163 WT 46 S2X30-12 WT 42 W94F 168 S2X35-11 WT 129 WT 133 S2X35-21 W50F 173 WT 133 S2X35-31 W109F 175 WT 133 S2X35-41 W50F-W109F-I110A 178 WT 133 S2X47-11 WT 52 WT 56 S2X47-21 W111F 186 WT 56 S2X47-12 WT 52 W92F-W99F 194 S2X47-33 W36F 189 W92F 196 S2X47-42 W36F-W111F 191 W92F-W99F 194 Example 8 S2H58 and S2N22 variant antibodies

Recombinant IgGl antibodies were generated using the VH and VL sequences of monoclonal antibodies S2H58 and S2N22 or their engineered variants. Combinations were generated as indicated in Table 21. Each of the antibodies was produced by transient transfection and expression of plastid vectors encoding recombinant antibodies in HD 293F cells (GenScript). Cells were harvested on day 4 and IgG performance was verified by Western blotting and protein A titer analysis. Table 21. Antibody VH (WT/ variant ) VH amino acid SEQ ID NO. VL (WT/ variant ) VL amino acid SEQ ID NO. S2H58-11 WT 228 WT 238 S2H58-21 W50F 350 WT 238 S2H58-31 W50F-S55A 351 WT 238 S2H58-32 W50F-S55A 351 V34G 355 S2H58-43 W50F-S55A-L102A 353 M94I 357 S2N22-11 WT 312 WT 316 S2N22-21 N56Q 359 WT 316 S2N22-31 N56G 361 WT 316 S2N22-41 T58A 363 WT 316 S2N22-51 Y57P 365 WT 316 S2N22-61 T58A-S63A 367 WT 316 S2N22-71 T58A-S63A-M34I 368 WT 316 Example 9 S2E12 variant antibody

Recombinant IgGl antibodies were generated using the VH and VL sequences of monoclonal antibody S2E12 and its engineered variants. The V-region amino acid sequences of S2E12 and certain engineered S2E12 variants are summarized in Table 22. Table 22. Antibody VH amino acid SEQ ID NO. VL amino acid SEQ ID NO. S2E12 399 403 409_11_4_v2 399 738 409_11_4_v3 399 744 409_11_4_v4 399 746 409_11_4_v5 748 403 409_11_4_v6 749 403 409_11_4_v7 750 403 409_11_4_v8 752 403 409_11_4_v9 754 403 409_11_4_v10 756 403 409_11_4_v11 758 403 409_11_4_v12 759 403 409_11_4_v13 761 403 Example 10 Neutralization of SARS- CoV -2 by recombinant antibodies

Human monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested against SARS-CoV-2 pseudopatterned virus (VSV) in neutralization assays.

Recombinant monoclonal antibodies were serially diluted and incubated with a constant amount of VSV-deltaG-luc pseudopatterned with SARS-CoV-2 (strain βCoV/Wuhan-Hu-1/2019, accession number MN908947) at 37°C for 1.5 Hour. VeroE6 cells were then added to complete DMEM medium and the plates were incubated at 37°C for 24 hours. To measure the amount of luciferase expressed in infected cells, the medium was aspirated and the luciferase substrate, Bio-Glo Luciferase Assay System (Promega AG), warmed to room temperature was added. After 10 min incubation on a shaker in the dark, the signal was measured in a luminometer using a 1 second integration time.

Results for certain monoclonal antibodies are shown in Figures 12A-12D. Calculated IC50 and IC90 values (ng/ml) are shown below each figure. Example 11 Binding of antibodies to RBD using Octet

The binding affinity and avidity of antibodies S2X193, S2X195, S2X219, S2X244, S2X246, S2X256, S2X269 and S2X278 for SARS-CoV-2 RBD were measured by Octet. The antibody was loaded onto the Protein A needle at 2.7 µg/ml. SARS-CoV-2 RBD was loaded at 6 µg/ml, 1.5 µg/ml or 0.4 µg/ml for 5 minutes. Dissociation was measured for 7 minutes. The results are shown in Figures 14A-14H. In each figure, the vertical dashed line indicates the start of the dissociation period.

The binding affinity and avidity of antibodies S2X193, S2X195, S2X219, S2X244, S2X246, S2X256, S2X269 and S2X278, as well as four comparative antibodies to SARS-CoV-1 RBD were also measured by Octet. The antibody was loaded onto the Protein A needle at 2.7 µg/ml. The SARS-CoV-1 RBD was loaded at 6 µg/ml for 5 minutes. Dissociation was measured for 7 minutes. The results are shown in FIG. 15 . In each figure, the vertical dashed line indicates the start of the dissociation period. Example 12 Quantitative epitope- specific serology of the SARS-CoV-2 spike protein

SARS-CoV-2 spike protein antibody binding was analyzed by antibody competition analysis, cryo-EM data and crystallographic data. From this analysis, the spike protein RBD antigenic sites Ia, Ib, Ic, Id, II and IV were identified. A graph representing these sites and antibodies bound within each site is shown in FIG. 24 . Example 13 Binding of S2E12 antibody to SARS - CoV - 2 RBD

Binding of S2E12 and S2E12 variant antibodies to SARS-CoV-2 RBD was measured by surface plasmon resonance (SPR). SPR experiments were performed with a Biacore T200 instrument using the single-cycle kinetic method. Antibodies were captured on the surface and increasing concentrations of purified SARS-CoV-2 RBD were injected. Association and dissociation kinetics were monitored and fitted to binding models to determine affinity.

The results are shown in Tables 23 and 24. Antibody "S2E12-11" was obtained from the supernatant of CHO cells transformed to express S2E12 antibody. Antibody S2E12 WT (VH of SEQ ID NO.:399, VL of SEQ ID NO.:403) was generated using purified antibody produced in transformed HEK cells. KD/KD_WT lists the KD value of the indicated antibody divided by the KD value of S2E12 WT. KD_WT/KD lists the KD value of S2E12 WT divided by the KD value of the indicated antibodies. Blank cells indicate that no binding was measured using this assay. Table 23. Antibody Ka (1/Ms) Kd (1/s) KD (M) KD/KD_WT S2E12 WT 1.98E+06 0.002335 1.18E-09 1.0 S2E12-11 2.42E+06 0.003174 1.31E-09 1.1 409_11_4_v5 2.68E+06 0.03576 1.33E-08 0.098 409_11_4_v3 1.18E+06 0.01527 1.30E-08 0.100 409_11_4_v7 1.86E+06 0.009129 4.90E-09 0.267 409_11_4_v8 409_11_4_v9 409_11_4_v10 409_11_4_v11 Table 24. Antibody KD (M) [ Phase 1 ] KD_WT/KD S2E12 WT 2.28E-09 1.00 409_11_4_v4 2.59E-08 0.09 409_11_4_v2 7.88E-10 2.89 409_11_4_v6 2.04E-08 0.11 409_11_4_v12 4.53E-08 0.05 409_11_4_v13 5.14E-08 0.04 Example 14 ACE2 -Independent Mechanisms of SARS - CoV -2 Neutralization by Antibodies

To study the mechanism of antibody neutralization of SARS-CoV-2 infection. In the following experiments, unless otherwise specified, the S309 antibody (VH of SEQ ID NO.: 139, VL of SEQ ID NO.: 143) is represented as recombinant IgGl with M428L and N434S mutations. To investigate the effect of ACE2 overexpression on S309 antibody neutralization of infection. Vero E6 or Vero E6-TMPRSS2 cells were transfected with SARS-CoV-2 (isolate USA-WA1/2020) at MOI 0.01 in the presence of S309 (10 µg/ml). Cells were fixed 24 h after infection, and viral nucleocapsid proteins were immunostained and quantified. Nucleocapsid staining was effectively absent in antibody-treated cells. The IC50 (ng/ml) of S309 was 65 in Vero E6 cells and 91 in Vero E6-TMPRSS2 (data not shown).

A set of seven cell lines (HeLa, 293T (wt), Vero E6, Huh7, 293T ACE2, MRC 5-ACE2-TMPRSS2, A549-ACE2-TMPRSS2 clone 5, A549-ACE2-TMPRSS2 clone 10) were processed in the presence of S309. SARS-CoV-2-Nluc or VSV pseudopatterned with the SARS-CoV-2 spike protein was transfected. Luciferase signal was quantified 24 h after infection. The S309 maximum neutralization value is shown in Table 25. Table 25. Maximum Neutralization Value for S309 cell type Virus/pseudotype specimen SARS-CoV-2-Nluc VSV pseudotype specimen Vero E6 >99% >99% Vero E6-TMPRSS2 >99% 96% Huh7 98% 78% 293T ACE2 26% 34% MRC5-ACE2-TMPRSS2 87% 45% A549-ACE2-TMPRSS2 pure line 5 89% 65% A549-ACE2-TMPRSS2 pure line 10 81% 42%

S2E12 neutralization data are shown in Figure 53 (SARS-CoV-2-Nluc) and Figure 54 (pseudo-patterned VSV). Notably, S2E12 exhibited comparable neutralizing activity on all target cells.

Binding of purified fluorescently labeled SARS-CoV-2 spike protein to these cell lines was quantified by flow cytometry. HeLa and 239T WT cells already had the lowest MFI, followed by Huh7 and VeroE6 cells. 293T ACE2 cells (highest), MRC 5-ACE2-TMPRSS2 (third highest), A549-ACE2-TMPRSS2 clone 5 (fourth highest) and A549-ACE2-TMPRSS2 clone 10 (second highest) had higher MFIs. A correlation analysis between the maximal neutralization potential of S309's spike protein binding was determined; the S309 Spearman correlation value for both virus models was r = -0.94. p=0.017. See Figure 55.

To further characterize SARS-CoV-2 sensitive cell lines, the seven cell lines described above were incubated with purified fluorescently labeled SARS-CoV-2 spike protein or RBD protein and analyzed by flow cytometry Measurements quantify protein binding. In descending order of MFI, the cell lines were: A549-ACE2-TMPRSS2 clone 10; 293T ACE2; MRC 5-ACE2-TMPRSS2; A549-ACE2-TMPRSS2 clone 5; Vero E6; Huh7; 293T (wt); and HeLa.

Selected lectins and disclosed receptor candidates were screened using HEK293T cells transfected with SARS-CoV-2 VSV pseudovirus. ACE2, DC-SIGN, L-SIGN and SIGLEC-1 get the highest signal. ACE2 provides signals of about 10 ⁵ relative light emitting units (RLU), and DC-SIGN, SIGLEC-1 and L-SIGN have signals of about 10 ⁴ RLUs. All other lectins/candidates tested gave signals ^of approximately ^102-103 RLUs.

HEK 293T, HeLa and MRC5 were transiently transduced to overexpress DC-SIGN, L-SIGN, SIGLEC1 or ACE2 and transfected with SARS-CoV-2 VSV pseudovirus. Uninfected and untransduced cells were included as controls. In HEK293T cells, ACE2, DC-SIGN, SIGLEC-1 and L-SIGN all caused substantial increases in infection. In HeLa and MRC5 cells, only ACE2 increased infection.

Stable HEK293T cell lines overexpressing DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 were reliably transfected with SARS-CoV-2 (MOI 0.1), fixed and targeted for SARS-CoV-2 nucleoprotein at 24 hours Immunostaining was performed. Wild-type cells (infected and uninfected) were used as controls. Increased staining was observed in cells overexpressing DC-SIGN, L-SIGN or SIGLEC-1 and significantly increased in cells overexpressing ACE2.

Stable cell lines were transfected with SARS-CoV-2-Nluc and luciferase levels were quantified at 24 hours. In ascending order of RLU: uninfected (about 10 ² -10 ³ RLU); parent 293T (about 10 ⁴ RLU); DC-SIGN (about 10 ⁵ RLU); L-SIGN (about 10 ⁵ RLU); SIGLEC-1 (approximately ^105-106 RLU) ^; ACE2 (> ¹⁰⁷ RLU).

Stable cell lines were incubated with various concentrations of anti-SIGLEC1 mAb (clone 7-239) and transfected with SARS-CoV-2-Nluc. Infection as a percentage of untreated cells remained almost over 100% in 293T cells expressing DC-SIGN, L-SIGN or ACE2, but dropped below 50% in 293T cells expressing SIGLEC-1 (0.2 μg/mL anti- SIGLEC) to nearly 0 (1 μg/mL or 5 μg/mL anti-SIGLEC).

Determination of single-cell expression levels of selected potential SARS-CoV-2 (co)receptor candidates in different lung cell types derived from the human lung cell Atlas (nature.com/articles/s41586-020-2922-4) . DC-SIGN, L-SIGN and SIGLEC-1 are expressed in multiple cell types in the lung at similar or even higher levels than ACE2.

Binding of antibodies targeting DC-/L-SIGN, DC-SIGN, SIGLECl or ACE2 on HEK293T cells stably overexpressing the corresponding adhesion receptors was analyzed by flow cytometry and immunofluorescence analysis. HEK 293T cells overexpressing the corresponding adhesion receptors were transfected with SARS-CoV-2 wild-type Spike protein or VSV pseudopatterned carrying the B1.1.7 lineage Spike protein. Luminescence was analyzed one day after infection. Infection is increased in cells expressing adhesion receptors. Infection by spike protein pseudopatterned VSV was similar for each test group. Cells expressing ACE2 received the highest luminescent signal.

In vitro differentiated moDC or PBMC Vero E6 cells were transfected with SARS-CoV-2 at MOI 0.01. At 24 h post infection, cells were fixed, immunostained for viral nucleocapsid proteins and infected cells were quantified. Only VeroE6 cells showed infection (about 7% cells). Infected cell supernatants were taken at 24, 48 and 72 h and infectious virus titers were quantified by FFU analysis on Vero E6 cells.

The main cell types with detectable SARS-CoV-2 gene bodies were assessed in bronchoalveolar lavage fluid (BALF) and sputum of patients with severe COVID-19. t-SNE curves were obtained and counts were determined for each SARS-CoV-2+ cell type (total n=3,085 cells from 8 individuals in Ren et al. Cell 2021). Cell types were T, NK, plasma, neutrophils, macrophages, cilia, squamous and secretory cells. The performance of ACE2, DC-SIGN, L-SIGN, SIGLEC-1 and combinations of these was assessed for each cell. Figures 65-66.

ACE2, DC-SIGN (CD209), L-SIGN (CLEC4M), SIGLEC1 transcript counts correlated with SARS-CoV-2 RNA counts in macrophages and secretory cells. Correlations are based on counts from Ren et al. Cell 2021 (before log transformation).

Representative data showing the performance of the receptor in the stable HEK293T cell line is shown in FIG. 41 .

Representative data using luminescence assays to assess the ability of a VSV pseudovirus exhibiting the SARS-CoV-2 S protein of the luciferase reporter to infect HEK293T cells is shown in Figure 42 (see also Figure 57); DC-SIGN or L The expression of -SIGN increased the level of pseudovirus infection by more than 10-fold compared to the infection of WT HEK293T cells, and the expression of ACE2 increased the level of pseudovirus infection by more than 100-fold compared to the infection of WT HEK293T cells.

The neutralizing activity of mAb S309 against VSV pseudovirus was assessed in engineered HEK293T cells. Data are shown in Figure 43; S309 completely neutralized infection via DC-SIGN and L-SIGN, and to a lesser extent via ACE2.

The ability of live SARS-CoV-2 to infect HEK293T cells using the luciferase reporter was detected using a luminescence assay. The data are shown in Figure 44; expression of DC-SIGN or L-SIGN increased the level of live virus infection more than 3-fold compared to infection of WT HEK293T cells, and expression of ACE2 increased the level of live virus infection to that of WT HEK293T cells. Infections increased more than 100-fold compared to See also Figure 58, showing infection as determined by staining for SARS-CoV-2 nucleoprotein.

The neutralizing activity of S309 against VSV pseudovirus was assessed in engineered HEK293T cells. Data are shown in Figure 45; S309 completely neutralized infection via DC-SIGN and L-SIGN, and to a lesser extent via ACE2.

Experiments were performed to investigate whether S309 or S2E12 antibodies could neutralize SARS-CoV-2 entry via SIGLEC-1. In the following experiments, the S309 antibody (VH of SEQ ID NO.:139, VL of SEQ ID NO.:143) and S2E12 antibody (VH of SEQ ID NO.:399, VL of SEQ ID NO.:403) are represented as Recombinant IgG1 with M428L and N434S mutations. Briefly, a stable HEK293T strain of cells was generated as described above to overexpress DC-SIGN/L-SIGN, DC-SIGN, SIGLEC-1 or ACE2. Performance data is shown in Figure 46. As shown in Figure 47, expression of DC-SIGN, L-SIGN or SIGLEC increased live virus infection levels more than 10-fold compared to infection of WT HEK293T cells, and expression of ACE2 increased pseudovirus infection levels compared to WT HEK293T cells infection was increased by more than 100 times. As shown in Figure 48, S309 completely neutralized infection via DC-SIGN, L-SIGN and SIGLEC-1. As shown in Figure 49, S2E12 completely neutralized infection via SIGLEC-1 and ACE2.

Expression of DC-SIGN (CD209) and other cell surface receptor proteins including SIGLEC-1 and other SIGLECs was determined on various cell types. The data are summarized in Figures 50A and 50B.

Additional experiments were performed to investigate the function of DC-SIGN, L-SIGN and SIGLEC-1 in SARS-CoV-2 infection. In one set of experiments, HEK293T cells stably expressing DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 were transfected with live SARS-CoV-2 Nluc at three different infection folds (MOI: 0.01, 0.1 and 1). Infection was determined using relative luminescence cells and compared to infection in HEK293T cells (parent). The data are shown in Figure 51. At the lowest MOI tested, an increase in infection was observed in DC-SIGN, L-SIGN or SIGLEC. At the highest MOI tested, infection was not further increased by expression of DC-SIGN, L-SIGN or SIGLEC compared to parent. These data indicate that parental 293T cells are susceptible to infection by SARS-CoV-2 and that L-SIGN, DC-SIGN and SIGLEC-1 increase the level of infection but do not act as primary receptors for infection.

In another set of experiments, 293T cells, HeLa cells and MRC5 cells were transiently transduced with lentivirus encoding DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 and transfected with VSV pseudovirus three days after transduction. The data are shown in Figure 52. 293T cells showed lower levels of susceptibility (compare uninfected versus untransduced), while HeLa and MRC5 cells were completely resistant to the virus. Lower infection levels in 293T cells could be increased by the expression of L-SIGN, DC-SIGN or SIGLEC-1, consistent with the role of these proteins as adhesion factors. HeLa and MRC5 cells remained resistant to infection even after expression of L-SIGN, DC-SIGN or SIGLEC-1 and became susceptible only after expression of ACE2. These data indicate that L-SIGN, DC-SIGN and SIGLEC-1 are not the primary receptors for SARS-CoV-2.

Further neutralization assays for counter-infection, cell-cell fusion and infection were performed. Figure 71 shows neutralization on Vero E6 cells using antibodies S309, S2E12 and S2X333. Figure 72 shows neutralization on Vero E6-TMPRSS2 cells using the same antibodies. Figures 75 and 76 show neutralization of infection by these antibodies on various cell types. Figures 77-80 show results from cell-cell fusion and fusion inhibition assays. Figures 81-84 show neutralization by infection with antibodies on stable HEK293T cell lines overexpressing ACE2, SIGLECl, DC-SIGN or L-SIGN. Example 15 In vivo efficacy of S309 antibody and combinations of S309 and S2E12 antibodies

The efficacy of S309 and the combination of S309 and S2E12 was studied in Syrian hamsters. This animal model represents the most relevant model of SARS-CoV-2 infection to date that does not require in vivo overexpression of ACE2 to support toxigenic infection and disease. Prophylactic administration of S309 induced dose-dependent protection against SARS-CoV-2 infection and tissue damage in hamsters, as indicated by viral RNA levels, viral load, and histopathological scores in the lungs (Figure 56A, left column). These data indicate that poor and incomplete neutralization of in vitro entry by S309 does not compromise the in vivo efficacy of non-RBM mAbs when using ACE2 overexpressing cells. Similar results were obtained using the combination of S309 and S2E12 antibodies (FIG. 56A, right column).

S309 carrying the N297A mutation has a reduced ability to trigger effector functions due to reduced engagement with Fcγ receptors. This was further confirmed by the reduced binding of the S309-N297A variant to hamster monocytes in the spleen. The in vivo efficacy measured with the N297A mAb was similar or only slightly inferior to that of wt S309, indicating that the neutralizing ability of the mAb outperformed its effector function under these conditions. The serum concentration of S309 required to reduce viral RNA in the lung by 90% was 9 µg/ml (Figure 56B, left column). Similar results were obtained using the combination of S309 and S2E12 antibodies (FIG. 56B, right column). Example 16 Further in vivo studies using the S2E12 - v2 antibody

Preclinical studies were performed using non-human primates to assess S2E12-v2 having the VH amino acid sequence of SEQ ID NO: 399 and the VL amino acid sequence of SEQ ID NO: 738 and comprising M428L and N434S Fc mutations (Fig. 99 as "S2E12") pharmacokinetics and potential tissue cross-reactivity safety. As shown in Figures 99 and 100, the mean T _1/2 for S2E12-v2 MLNS at a single 5 mg/kg dose was 25.4 days (between 3 animals). Tissue cross-reactivity studies (using CHO-CoV2-S Spike, 1:1 CHO-CoV2S-Spike:CHO, and CHO as controls) did not identify any tissues at 1.25, 0.3125, or 0.078125 μg/ml Among them were cross-reactive staining by S2E12-v2. Example 17 Further neutralization studies

To investigate the potential effect of known SARS-CoV-2 mutations on S2E12 neutralization efficacy. The following individual mutations in SARS-CoV-2 S have less than 3-fold reduction in neutralization of S2E12 against live SARS-CoV-2 or SARS-CoV-2 pseudovirus: N501Y; S477N; N439K; L452R; E484K ; K417N; T478K; S494P; A520S; N501T; A522S; Y453F; P384L. Example 18 Materials and Methods Flow Cytometry-Based Screening for Binding to CoV S Protein Expressed on Mammalian Cells

ExpiCHO cells were transfected with the S protein of SARS-CoV-2. The monoclonal antibodies were then tested by flow cytometry at 10 µg/ml for their ability to stain ExpiCHO cells expressing the S protein of SARS-CoV-2 transfectants. Temporary performance of recombinant SARS-CoV-2 protein

The full-length S gene (Accession No. MN908947) of the SARS-CoV-2 strain (2019-nCoV-S) isolate βCoV/Wuhan-Hu-1/2019 was codon-optimized for human cell performance and cloned into phCMV1 expression vector (Genlantis). Expi-CHO cells were transfected with phCMV1-SARS-CoV-2-S, phCMV1-MERS-CoV-S (London1/2012), SARS-Spike_pcDNA.3 (strain SARS) or empty phCMV1 using the Expifectamine CHO enhancer (Mock) transiently transfected. Two days after transfection, cells were harvested, fixed, or fixed with saponin and pre-infiltrated for immunostaining with a panel of monoclonal antibodies reactive against the SARS-CoV receptor binding domain (RBD). Alexa647-labeled secondary antibody anti-human IgG Fc was used for detection. Antibody binding to transfected cells was analyzed by flow cytometry using a ZE5 cell analyzer (Biorard) and FlowJo software (TreeStar). Positive binding was defined by differential staining of CoV-S-transfectants relative to mock-transfectants. Competition experiments using Octet (BLI , Biolayer Interferometry )

Unless otherwise specified herein, an anti-His sensor (BIOSENSOR ANTI-PENTA-HIS (HIS1K)) was used to immobilize the S1 subunit protein of SARS-CoV (Sino Biological Europe GmbH). The sensor was hydrated with kinetic buffer (KB; 0.01% endotoxin-free BSA, 0.002 Tween-20, 0.005% NaN3 in PBS) for 10 min. The SARS-CoV S1 subunit protein was then loaded in KB at a concentration of 10 µg/ml for 8 min. Antibodies were associated at 15 µg/ml for full-length mAbs nCoV-10 and nCov-6 mAbs, or 5 µg/ml for Fab nCoV-4 for 6 min, and nCoV-1 contained at 10 µg/ml in all consecutive experiments. Competing antibodies were then allowed to associate at the same concentration for a further 6 min. Competition experiments using Octet (BLI , Biolayer Interferometry )

For ACE2 competition experiments, ACE2-His (Bio-Techne AG) was loaded onto an anti-HIS (HIS2) biosensor (Molecular Devices-ForteBio) at 5 μg/ml in KB for 30 minutes. SARS-CoV-1 RBD-rabbit Fc or SARS-CoV-2 RBD-mouse Fc (Sino Biological Europe GmbH) was incubated at 1 µg/ml after preincubation with or without antibody (30 µg/ml, 30 min). 15 minutes of association under ml. Dissociation was monitored for 5 minutes. Affinity determination using Octet (BLI , Biolayer Interferometry )

For KD determination of full-length antibodies, recombinant antibodies were immobilized at 2.7 μg/ml for 1 min using a protein A biosensor (Pall ForteBio) following a 10 min hydration step with kinetic buffer. By using different concentrations of SARS-CoV-1 RBD (Sino Biological) or SARS-CoV-2 RBD (in-house generated; residues 331-550 of the spike protein from βCoV/Wuhan-Hu-1/2019, accession number MN908947) incubate the antibody-coated sensor to record the association curve for 5 minutes. The highest RBD concentration tested was 10 ug/ml followed by a 1:2.5 serial dilution. Dissociation was recorded for 9 minutes by moving the sensor to the well containing the KB. KD values were calculated using an overall fitted model (Octet). Octet Red96 (ForteBio) equipment was used.

For _KD determination of full-length antibodies compared to Fab fragments, HIS-tagged RBDs of SARS-CoV-1 or SARS-CoV-2 were loaded in KB at 3 µg/ml for anti-HIS (HIS2) biosensing device (Molecular Devices, ForteBio) for 15 minutes. Association of full-length antibody to Fab was performed in KB at 15 ug/mL and 5 ug/mL, respectively, for 5 minutes. Dissociation in KB was measured for 10 minutes. ELISA binding

The reactivity of mAbs with the SARS-CoV-2 spike S1 subunit protein (strain WH20) protein was determined by enzyme-linked immunosorbent assay (ELISA). Briefly, 96-well plates were coated with 3 µg/ml recombinant SARS-CoV-2 spike protein S1 subunit protein (Sino. Biological). Wells were washed and blocked with PBS + 1% BSA for 1 hour at room temperature and then incubated with serially diluted mAbs for 1 hour at room temperature. Bound mAbs were detected by incubating alkaline phosphatase-conjugated goat anti-human IgG (Southern Biotechnology: 2040-04) for 1 hr at room temperature, and were assayed with 1 mg/ml p-nitrophenyl phosphate. Development was performed in 0.1 M glycine buffer (pH 10.4) at room temperature for 30 minutes. Optical density (OD) values were measured at a wavelength of 405 nm in an ELISA reader (Powerwave 340/96 spectrophotometer, BioTek). Neutralization Analysis

Murine leukemia virus (MLV) pseudopatterned with SARS-CoV-2 spike protein (SARS-CoV-2pp) or SARS-CoV-1 spike protein (SARS-CoV-1pp) was used unless otherwise specified. DBT cells stably transfected with ACE2 (DBT-ACE2) were used as target cells. SARS-CoV-2pp or SARS-CoV-1pp were activated with trypsin TPCK at 10 ug/ml. Activated SARS-CoV-2pp or SARS-CoV-1pp was added to serial dilutions of antibodies (starting at 50 ug/ml final concentration/antibody, 3-fold dilution). DBT-ACE2 cells were added to the antibody-virus mixture and incubated for 48 hours. Luminescence was measured after aspiration of cell culture supernatant and addition of stable-GLO substrate (Promega).

Unless otherwise specified, pseudoparticle neutralization assays used the VSV-based luciferase reporter pseudo-patterning system (Kerafast). VSV pseudoparticles and antibodies were mixed in DMEM and allowed to incubate at 37°C for 30 minutes. The infection mixture was then incubated with Vero E6 cells for 1 h at 37°C, followed by the addition of DMEM with penicillin-streptomycin and 10% FBS (infection mixture was not removed). Cells were incubated at 37°C for 18-24 hours. Luciferase was measured using an Ensight disc reader (Perkin Elmer) after addition of Bio-Glo reagent (Promega). SPR Single Cycle Kinetics

SPR experiments were performed with a Biacore T200 instrument using the single-cycle kinetic method. S309 IgG was captured on the surface and increasing concentrations of glycosylated or deglycosylated purified SARS-CoV-2 RBD were injected. Association and dissociation kinetics were monitored and fitted to binding models to determine affinity. Expression of recombinant antibodies Recombinant antibodies were expressed in ExpiCHO cells transiently co-transfected with plastids expressing heavy and light chains as previously described. (Stettler et al. (2016) Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection. Science, 353(6301), 823-826). Monoclonal antibodies S303, S304, S306, S309, S310 and S315 are denoted as rIgG-LS antibodies. LS mutations confer a longer half-life in vivo. (Zalevsky et al. (2010) Enhanced antibody half-life improves in vivo activity. Nature Biotechnology, 28(2), 157-159) Sequence alignment

The SARS-CoV-2 genomic sequence was downloaded from GISAID on March 29, 2020, using the "complete (>29,000 bp)" and "lower coverage exclusion filters". Remove bat and pangolin sequences to get human-only sequences. The spike protein ORF was mapped by reference protein (YP_009724390.1)-gene body alignment with GeneWise2. Incomplete matches and ORFs containing insertions or deletions were rescued and included in downstream analyses. Nucleotide sequences were translated using seqkit electronic hybridization. Sequences with more than 10% unidentified amino acids (due to N base calls) were removed. Multiple sequence alignments were performed using MAFFT. Variants were determined by comparing aligned sequences (n=2,229) to a reference sequence using R/Bioconductor packaged Biostrings. A similar strategy was used to extract and translate the spike protein sequence from the SARS-CoV genome derived from ViPR (search criteria: SARS-associated coronavirus, full-length genome, human host, deposited before December 2019 to exclude SARS-CoV -2, n=53). The source SARS-CoV genome sequence includes all major published strains such as Urbani, Tor2, TW1, P2, Frankfurt1 and others. The pangolin sequence as shown by Tsan-Yuk Lam et al. was derived from GISAID. The bat sequences from three clades of Sabei coronavirus as shown by Lu et al. (Lancet 2020) were derived from Genbank. Civet and raccoon dog sequences were similarly derived from Genbank. Generation of stable overexpressing cell lines

Lenti-X 293T was co-transfected with lentiviral expression plastids encoding DC-SIGN (CD209), L-SIGN (CLEC4M), SIGLEC1, TMPRSS2 or ACE2 (all obtained from Genecopoeia) and corresponding lentiviral helper plastids cells (Takara) to produce lentivirus. Forty-eight hours after transfection, the lentivirus in the supernatant was harvested and concentrated by ultracentrifugation at 20,000 rpm for 2 h. Lenti-X 293T (Takara), Vero E6 (ATCC), MRC5 (Sigma-Aldrich), A549 (ATCC) were transduced in the presence of 6 ug/mL polybrene (Millipore) for 24 hours. Cell lines overexpressing the two transgenic genes were then transduced. Selection with puromycin and/or blasticidin (Gibco) was initiated two days after transduction and selection reagents were maintained in growth medium for all subsequent cultures. A single cell clone was derived from the A549-ACE2-TMPRSS2 cell line, all other cell lines represent cell pools. SARS - CoV - 2 neutralization

Vero E6 or Vero E6-TMPRSS2 cells cultured in DMEM supplemented with 10% FBS (VWR) and 1x penicillin/streptomycin (Thermo Fisher Scientific) were seeded in black 96-well dishes at 20,000 cells/well. Serial 1:4 dilutions of monoclonal antibodies were combined with 200 pfu of SARS-CoV-2 (isolate USA-WA1/2020, passage 3, passage 3, in Vero E6 cells at 37°C in a BSL-3 facility ) together for 30 minutes. The cell supernatant was removed and the virus-antibody mixture was added to the cells. 24 hours post-infection, cells were fixed with 4% paraformaldehyde for 30 minutes, followed by two PBS (pH 7.4) washes, and permeabilized with 0.25% Triton X-100 in PBS for 30 minutes. After blocking in 5% milk powder/PBS for 30 minutes, cells were incubated with a primary antibody targeting SARS-CoV-2 nucleocapsid protein (Sino Biological, cat. 40143-R001) at a 1:2000 dilution for 1 hour . After washing and incubation for 1 hour with secondary Alexa647-labeled antibody mixed with 1 μg/ml Hoechst33342, the discs were imaged on an automated cell imaging reader (Cytation 5, Biotek) and the software provided by the manufacturer was used Nucleocapsid-positive cells were counted. SARS - CoV - 2 - Nluc neutralization

Neutralization was determined using an infectious clone of SARS-CoV-2-Nluc, an infectious clone of SARS-CoV-2 (based on strain 2019-nCoV/USA_WA1/2020) encoding nanoluciferase but not viral ORF7, which showed that Growth kinetics comparable to wild-type virus (Xie et al., Nat Comm, 2020, https://doi.org/10.1038/s41467-020-19055-7). Cells were seeded at 20,000 cells/well into black-walled, clear-bottomed 96-well dishes (293T cells were seeded at 35,000 cells/well into poly-L-lysine-coated wells) and incubated at 37°C Incubate overnight. The next day, 9 point 4-fold serial dilutions of the antibody were prepared in infection medium (DMEM + 10% FBS). SARS-CoV-2-Nluc was diluted in infection medium at the indicated MOI, added to antibody dilution and incubated at 37°C for 30 min. Media was removed from cells, mAb-virus complexes were added, and cells were incubated at 37°C for 24 hours. Media was removed from cells, Nano-Glo luciferase substrate (Promega) was added according to the manufacturer's recommendations, incubated for 10 min at room temperature, and fluorescence was quantified on a VICTOR Nivo disc reader (Perkin Elmer) luciferase signal. SARS-CoV-2 pseudopatterned VSV production and neutralization

To generate SARS-CoV-2 pseudopatterned vesicular stomatitis virus, Lenti-X 293T cells (Takara) were seeded in 10-cm dishes until 80% confluent the next day. The following day, cells were transfected with plastids encoding the SARS-CoV-2 S-glycoprotein (YP_009724390.1) containing a C-terminal 19 aa truncation using TransIT-Lenti (Mirus Bio) according to the manufacturer's instructions. One day after transfection, cells were infected with VSV (G*ΔG-luciferase) (Kerafast) at an MOI of 3 infectious units/cell. The viral inoculum was washed off after one hour and the cells were incubated for an additional day at 37°C. Cell supernatants containing SARS-CoV-2 pseudo-patterned VSV were collected on day 2 post-transfection, centrifuged at 1000 x g for 5 min to remove cellular debris, aliquoted and frozen at 80°C.

For virus neutralization, cells were seeded at 20,000 cells/well into black-walled, clear-bottomed 96-well dishes (293T cells were seeded at 35,000 cells/well into poly-L-lysine-coated wells) and incubated overnight at 37°C. The following day, 9:4 serial dilutions of the antibody were prepared in culture medium. SARS-CoV-2 pseudo-patterned VSV was diluted 1:30 in medium in the presence of 100 ng/mL anti-VSV-G antibody (clone 8G5F11, absolute antibody) and added 1:1 to each antibody dilution. The virus:antibody mixture was incubated at 37°C for 1 hour. The medium was removed from the cells and 50 μL of virus:antibody mixture was added to the cells. One hour after infection, 100 μL of medium was added to all wells and incubated at 37°C for 17-20 hours. Media was removed and 50 μL of Bio-Glo reagent (Promega) was added to each well. The disks were shaken on a disk shaker at 300 RPM for 15 minutes at room temperature and the RLUs were read on an EnSight disk reader (Perkin-Elmer). Transfection-based Adhesion Receptor Screening

Lenti-X293T cells (Takara) were transfected with plastids (all purchased from Genecopoeia) encoding the following receptor candidates: ACE2 (NM_021804), DC-SIGN (NM_021155), L-SIGN (BC110614), LGALS3 (NM_002306), SIGLEC1 (NM_023068), SIGLEC3 (XM_057602), SIGLEC9 (BC035365), SIGLEC10 (NM_033130), MGL (NM_182906), MINCLE (NM_014358), CD147 (NM_198589), ASGR1 (NM_001671.4), ASGR2 (NM_080913), NRP1 (NM_003873 ). One day after transfection, cells were infected with SARS-CoV-2 pseudopatterned VSV at a 1:20 dilution in the presence of 100 ng/ml anti-VSV-G antibody (clone 8G5F11, absolute) at 37°C. One hour after infection, 100 μL of medium was added to all wells and incubated at 37°C for 17-20 hours. Media was removed and 50 μL of Bio-Glo reagent (Promega) was added to each well. The disks were shaken on a disk shaker at 300 RPM for 15 minutes at room temperature and the RLUs were read on an EnSight disk reader (Perkin-Elmer). Anti-infection

Parental HeLa cells or HeLa cells stably expressing DC-SIGN, L-SIGN or SIGLEC1 were seeded at 5,000 cells/well in black-walled, clear-bottomed 96-well dishes. One day later, cells reached approximately 50% confluency and were seeded at 1:10 dilution with SARS-CoV-2 pseudopatterned VSV in the presence of 100 ng/mL anti-VSV-G antibody (clone 8G5F11, absolute) at 37°C 2 hours. For antibody-mediated inhibition of counter-infection, cells were pre-incubated with 10 ug/mL anti-SIGLEC1 antibody (Biolegend, clone 7-239) for 30 min. After 2 h seeding, cells were washed four times with complete medium and 10,000 VeroE6-TMPRSS2 cells/well were added and incubated at 37°C for 17-20 h for counter-infection. Media was removed and 50 μL of Bio-Glo reagent (Promega) was added to each well. The disks were shaken on a disk shaker at 300 RPM for 15 minutes at room temperature and the RLUs were read on an EnSight disk reader (Perkin-Elmer). Cell - cell fusion of CHO-S cells CHO cells stably expressing the SARS-CoV-2 S-glycoprotein were seeded at 12'500 cells/well in 96-well dishes for microscopy, and in the second On the following day, various concentrations of mAb and nuclear marker Hoechst (final dilution 1:1000) were added to cells and incubated for an additional 24 hours. The degree of fusion was established using the Cytation 5 Imager (BioTek), and the nuclei were detected as objects and their size was measured using the object detection protocol. The nuclei of fused cells (ie, fused cells) were found to aggregate at the center of the fused cells and were identified as distinct larger objects, gated on their size. The area of objects in fused cells is divided by the total area of all objects multiplied by 100 to obtain the percentage of fused cells. Immunofluorescence analysis

After seeding with 4% paraformaldehyde for 30 min, HEK 293T cells were seeded onto poly-D-lysine coated 96-well plates (Sigma-Aldrich) and fixed for 24 hours, followed by two PBS (pH 7.4 ) and permeabilized with PBS containing 0.25% Triton X-100 for 30 min. Cells were incubated with primary antibodies anti-DC-SIGN/L-SIGN (Biolegend, cat. 845002, 1:500 dilution), anti-DC-SIGN (Cell Signaling, cat. 13193S, 1:500 dilution), anti-SIGLEC1 (Biolegend, cat. 346002, 1:500 dilution) or anti-ACE2 (R&D Systems, cat. AF933, 1:200 dilution) were incubated for 2 hours. After washing and incubation with secondary Alexa647-labeled antibody mixed with 1 ug/mL Hoechst33342 for 1 hour, the discs were imaged on a reverse fluorescence microscope (Echo Revolve). ACE2/TMPRSS2 RT-qPCR

RNA was extracted from cells using the NucleoSpin RNA Plus kit (Macherey-Nagel) according to the manufacturer's protocol. RNA was reverse transcribed using the High Capacity cDNA Reverse Transcription Kit (Applied Biosystems) according to the manufacturer's instructions. ACE2 (forward primer: CAAGAGCAAACGGTTGAACAC, reverse primer: CCAGAGCCTCTCATTGTAGTCT), HPRT (forward primer: CCTGGCGTCGTGATTAGTG, reverse primer: ACACCCTTTCCAAATCCTCAG) and TMPRSS2 were quantified using the Luna Universal qPCR master mix (New England Biolabs) according to the manufacturer's protocol (forward primer: CAAGTGCTCCRACTCTGGGAT, reverse primer: AACACACCGRTTCTCGTCCTC). The levels of ACE2 and TMPRSS2 were normalized to HPRT. HeLa cells were used as reference samples. All qPCRs were run on a QuantStudio 3 real-time PCR system (Applied Biosystems). SARS2 D614G spike protein production and biotin labeling

Using 293fectin as a transfection agent, pre-fused stabilized SARS2 D614G spike protein (containing the amino acid sequence Q14 to K1211) were transfected into HEK293 free-style cells. Cells were incubated at 37°C for three days for protein production. Subsequently, the supernatant was harvested by centrifuging the cells for 30 minutes at 500 xg, followed by a further 30 minutes of spinning at 4000 xg. Cell culture supernatants were filtered through 0.2 μM filters and loaded onto 5 mL C-tag affinity matrix columns, pre-equilibrated with 50 mM Tris pH 8 and 200 mM NaCl. The SARS2 D614G spike protein was eluted using 10 column volumes of 100 mM Tris, 200 mM NaCl and 3.8 mM SEPEA peptide. Elution peaks were concentrated and injected on a Superose 6 Plus 10/300 GL gel filtration column using 50 mM Tris pH 8 and 200 mM NaCl as operating buffer. SEC fractions corresponding to the monodisperse SARS2 D614G spike protein were collected and snap frozen in liquid nitrogen for storage at -80°C. The purified SARS2 D614G spike protein was biotinylated using the BirA500 biotin labeling kit auto-affinity pair. 5 ug BirA and 11 uL BiomixA and BiomixB were added to 50 μg Spike protein. The final spike protein concentration during the biotin labeling reaction was about 1 μM. The reaction was allowed to proceed at 4°C for 16 hours. Subsequently, the proteins were desalted using two Zeba spin columns pre-equilibrated with IX PBS pH 7.4. Flow cytometry analysis for DC-SIGN , L-SIGN , SIGLEC1 and ACE-2

HEK 293T cells expressing DC-SIGN, L-SIGN, SIGLEC1 or ACE2 were resuspended at 4x106 cells/mL and 100 μL/well were plated on V-bottom 96-well plates (Corning, 3894). The disks were centrifuged at 2,000 rpm for 5 minutes and washed with PBS (pH 7.4). Cells were resuspended in 200 μL of PBS containing Ghost violet 510 viability dye (Cell Signaling, cat. 13-0870-T100, 1:1,000 dilution), incubated on ice for 15 minutes and then washed. Cells were resuspended in cells containing at 1:100 dilution: mouse anti-DC/L-SIGN (Biolegend, cat. 845002), rabbit anti-DC-SIGN (Cell Signaling, cat. 13193), mouse anti-SIGLEC1 ( Biologend, cat. 346002) or goat anti-ACE2 (R&D Systems, cat. AF933) primary antibody in 100 μL of FACS buffer prepared with 0.5% BSA (Sigma-Aldrich) in PBS. After 1 hour incubation on ice, cells were washed twice and resuspended in Alexa Fluor-488-labeled secondary antibodies at a 1:200 dilution: goat anti-mouse (Invitrogen cat. A11001), goat anti-rabbit (Invitrogen cat. A11008) or donkey anti-goat (Invitrogen cat. A11055) in FACS buffer. After incubation on ice for 45 min, cells were washed three times with 200 μL of FACS buffer and fixed with 200 μL of 4% PFA (Alfa Aesar) for 15 min at room temperature. Cells were washed three times, resuspended in 200 μL of FACS buffer and analyzed by flow cytometry using a CytoFLEX flow cytometer (Beckman Coulter). Flow cytometry of SARS-CoV-2 spike protein and RBD bound to cells

Biotin-labeled SARS-CoV-2 spike protein D614G protein (Spikebiotin, produced in-house) or biotin-labeled SARS-CoV-2 spike protein receptor-binding domain (RBDbiotin, Sino Biological, 40592) at room temperature -V08B) with Alexa Fluor® 647 Streptavidin (AF647-strep, Invitrogen, S21374) in a 1:20 ratio by volume for 20 min. The labeled protein was then stored at 4°C until further use. Cells were dissociated with TrpLE Express (Gibco, 12605-010) and 105 cells were transferred to each well of a 96-well V-chassis (Corning, 3894). Cells were washed twice in flow cytometry buffer (2% FBS in PBS (w/o Ca/Mg)) and stained with Spikebiotin-AF647-strep at a final concentration of 20 µg/ml on ice Or stain with RBDbiotin-AF647-strep at a final concentration of 7.5 µg/ml for 1 h. Stained cells were washed twice with flow cytometry buffer, resuspended in 1% PFA (Electron Microscopy Sciences, 15714-S) and analyzed with Cytoflex LX (Beckman Coulter). Recombinant performance of SARS-CoV-2 -specific mAbs

Human mAbs were isolated from plasma cells or memory B cells of SARS-CoV-2 immunized donors as previously described. Recombinant antibodies were expressed in ExpiCHO cells at 37°C and 8% CO2. Cells were transfected using ExpiFect amine. Transfected cells were replenished 1 day after transfection with ExpiCHO feed and ExpiFectamine CHO enhancer. Cell culture supernatants were collected eight days after transfection and filtered through 0.2 μm filters. Recombinant antibodies were affinity purified using a 5 mL HiTrap™ MabSelect™ PrismA column on an ÄKTA xpress FPLC device, followed by a HiPrep 26/10 desalting column with histidine buffer (20 mM histidine, 8% sucrose, pH 6) Perform a buffer exchange. SARS - CoV - 2 Infection Model Virus Preparation in Hamsters

The SARS-CoV-2 strain βCov/Belgium/GHB-03021/2020 used in this study was recovered from nasopharyngeal swabs obtained from RT-qPCR-confirmed asymptomatic patients who returned from Wuhan, China in February 2020 (EPI ISL 109 407976|2020-02-03). The close relationship with the prototype Wuhan-Hu-1 2019-nCoV (GenBank Accession No. 112 No. MN908947.3) strain was confirmed by pedigree analysis. Infectious virus was isolated by serial passage on HuH7 and Vero E6 cells; passage 6 virus was used in the studies described herein. The titers of viral stocks were determined by endpoint dilution on Vero E6 cells using the Reed and Muench method. cell

Vero E6 cells (African green monkey kidney, African green monkey kidney, ATCC CRL-1586). Endpoint titrations were performed with medium containing 2% fetal bovine serum instead of 10%. SARS-CoV-2 infection model in hamsters

A hamster infection model for SARS-CoV-2 has been described previously. The specific study design is shown in the schematic below. Briefly, wild-type Syrian golden hamsters (Golden hamsters) were purchased from Janvier Laboratories and housed in ventilated isolation cages (IsoCage N Biocontainment system, Tecniplast) with ad libitum access to food and water and kept in the cages. enrichment (wood blocking). Animals were acclimated for 4 days prior to the start of the study. The rearing conditions and experimental procedures were approved by the Animal Experimentation Ethics Committee of the University of Leuven (License P065-2020). Female 6-8 week old hamsters were anesthetized with ketamine/xylazine/atropine and inoculated intranasally with 50 μL containing 2×106 TCID50 SARS-CoV-2 (day 0). treatment plan

Animals were treated prophylactically for 48 h prior to infection by intraperitoneal administration (ip) and monitored for appearance, behavior and body weight. On day 4 post-infection, hamsters were euthanized by intraperitoneal injection of 500 μL of Dolethal (200 mg/mL sodium pentobarbital, Vétoquinol SA). Lungs were collected and viral RNA and infectious virus were quantified by RT-qPCR and endpoint virus titration, respectively. Blood samples were collected for PK analysis prior to infection. SARS-CoV-2 RT-qPCR

Harvested lung tissue was homogenized in 350 μL RLT buffer (RNeasy Minikit, Qiagen) using bead disruption (Precellys) and centrifuged (10.000 rpm, 5 min) to collect cellular debris. RNA was extracted according to the manufacturer's instructions. Of the 50 μL of lysis buffer, 4 μL was used as template in RT-qPCR reactions. RT-qPCR was performed on the LightCycler96 platform (Roche) using the iTaq Universal Probe One-Step RT-qPCR Kit (BioRad) with N2 primers and probes targeting the nucleocapsid. SARS-CoV-2 cDNA (IDT) standards were used to represent viral genome copies per mg of tissue or per mL of serum. Endpoint virus titration

Lung tissue was homogenized in 350 μL of minimal minimal medium using bead disruption (Precellys) and centrifuged (10.000 rpm, 5 min, 4° C.) to collect cellular debris. To quantify infectious SARS-CoV-2 particles, end-point titrations were performed on confluent Vero E6 cells in 96-well dishes. Virus titers were calculated by the method of Reed and Muench using the Lindenbach calculator and expressed as 50% tissue culture infectious dose per mg of tissue (TCID50). Histology

For histological examination, lungs were fixed in 4% formaldehyde overnight and embedded in paraffin. Tissue sections (5 μm) were analyzed after staining with hematoxylin and eosin, and lung lesions were scored indiscriminately by specialized pathologists. The scoring parameters with a cumulative score of 1 to 3 are as follows: congestion, intraalveolar hemorrhage, apoptotic bodies in the bronchial wall, necrotizing bronchiolitis, perivascular edema, bronchial pneumonia, perivascular inflammation, perivascular inflammation, and vasculitis. Binding of immune complexes to hamster monocytes

Immune complexes (IC) were prepared by combining S309 mAb (hamster IgG, wt or N297A) with a biotinylated anti-idiotype Fab fragment and Alexa-488- produced by streptavidin. Serial dilutions of freshly viable hamster splenocytes obtained from untreated animals were incubated with pre-generated fluorescent ICs for 3 hours at 4°C. Cell binding was then assessed by cytometry while excluding dead cells and physically gating on monocyte populations. Results are expressed as the mean fluorescence intensity of Alexa-488 for the entire monocyte population. Bioinformatics Analysis

The processed Human Lung Cell Atlas (HLCA) data and cell type annotations were downloaded from Github (github.com/krasnowlab/HLCA). The processed single-cell transcriptome data and annotations of lung epithelial and immune cells from SARS-CoV-2 infected individuals were downloaded from the NCBI GEO database (ID: GSE158055) and Github (github.com/zhangzlab/covid_balf). Available sequence data from a second single-cell transcriptomic study by Liao et al. was downloaded from NCBI SRA (ID: PRJNA608742) for examining reads corresponding to viral RNA. The ratio of sgRNA to gene body RNA was estimated by counting TRS-containing reads supporting the leader-TRS junction. Guidelines and methods for detecting lead-TRS junction reads were adapted from Alexandersen et al. The viral genome reference and TRS annotation were based on Wuhan-Hu-1 NC_045512.2/MN908947 ⁴⁹ . Only 2 samples from individuals with severe COVID-19 had detectable leader-TRS junction reads (SRR11181958, SRR11181959).

The various embodiments described above can be combined to provide other embodiments. All U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications, and non-patent publications referenced in this specification and/or listed in this application fact sheet, including May 8, 2020 US Patent Application No. 63/022,392, filed May 13, 2020, US Patent Application No. 63/024,372, filed May 13, 2020, US Patent Application No. 63/027,814, filed May 20, 2020, 2020 US Patent Application No. 63/029,338, filed on May 22, 2020, US Patent Application No. 63/031,286, filed May 28, 2020, and US Patent Application No. 63/, filed on June 1, 2020 US Patent Application No. 033,045, filed June 9, 2020, US Patent Application No. 63/036,683, filed June 16, 2020, US Patent Application No. 63/039,939, filed June 30, 2020 Case No. 63/046,465, US Patent Application No. 63/057,767, filed July 28, 2020, US Patent Application No. 63/090,667, filed October 12, 2020, November 13, 2020 U.S. Patent Application No. 63/113,450, filed Feb. 25, 2021, and U.S. Patent Application No. 63/170,368, filed April 2, 2021, are in full text Incorporated herein by reference. As necessary, aspects of the embodiments may be modified to employ the concepts of various patents, applications, and publications to provide yet further embodiments.

These and other changes can be made to the embodiments in light of the above embodiments. In general, in the following claims, the terms used should not be construed to limit the scope of the claims to the specific embodiments disclosed in this specification and the claims, but should be construed to include all possible embodiments and the application The patent scope is entitled to the full scope of equivalents to which it is entitled. Therefore, the scope of the patent application is not limited by the present invention.

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1A-1D show the binding of certain antibodies to the SARS-CoV-2 spike protein RBD and the SARS-CoV-1 spike protein RBD. Human monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested for RBD binding by ELISA. Figure 1A shows the binding of five antibodies, Figures IB and 1C each show the binding of seven antibodies, and Figure ID shows the binding of four antibodies. The top two antibodies in Figure IB are shown with black symbols. In Figure IB, S2X28 binding is represented by a line that maintains or near zero OD over the entire range of concentrations tested. In Figure IB (top), S2X41 binding is represented by a curve with an EC50 of about 20.01 ng/ml. In each of Figures 1A-1D, the upper panel shows binding to the SARS-CoV-2 RBD, and the lower panel shows binding to the SARS-CoV-1 RBD. Boxes to the right of each figure (if present) indicate calculated EC50 values for the indicated antibodies.

Figure 2 shows inhibition of SARS-CoV-2 RBD binding to human ACE2 by recombinantly expressed monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection. ELISA plates were coated with recombinant human ACE2 (generated in-house). Coating was performed with ACE2 at 2 ug/ml in PBS. The plates were incubated overnight at 4°C and blocked with the blocking agent casein (1% casein from Thermofisher) for 1 hour at room temperature.

3A-3F show the results of infection neutralization assays using certain antibodies against SARS-CoV-2 pseudo-patterned virus. Monoclonal antibodies isolated from patients who recovered from SARS-CoV-2 infection were expressed recombinantly and tested in neutralization assays against murine leukemia virus (MLV) pseudo-patterned with the SARS-CoV-2 spike protein. Figure 3A shows the results for three antibodies. Figures 3B-3F each show the results for the four antibodies. Antibodies were tested at the concentrations indicated in the x-axis. The box to the right of each figure (if present) indicates the calculated IC50 of the indicated antibody.

Figures 4A-4N show the binding of other antibodies to SARS-CoV-2 spike protein, SARS-CoV-2 spike protein RBD, and SARS-CoV-1 spike protein RBD. Monoclonal antibody systems isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested for RBD binding by ELISA. The boxes to the right of each figure indicate the calculated EC50 values for the indicated antibodies.

Figures 5A-5D show the results of infection neutralization assays using additional antibodies against SARS-CoV-2 pseudo-patterned virus. Monoclonal antibodies isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and in neutralization assays (one antibody/assay) against murine leukemia virus pseudopatterned with the SARS-CoV-2 spike protein (MLV) for testing. Figures 5A and 5C each show the results for three antibodies. Figure 5B shows the results for two antibodies and Figure 5D shows the results for four antibodies. Antibodies were tested at the concentrations indicated on the x-axis. The box to the right of each figure (if present) indicates the calculated EC50 of the indicated antibody.

Figures 6A and 6B show the results of an infection neutralization assay using monoclonal antibodies against a reliable SARS-CoV-2 virus. Comparative antibody "S309-v2" comprises the VH amino acid sequence set forth in SEQ ID NO.: 342 and the VL amino acid sequence set forth in SEQ ID NO.: 346 (respectively as SEQ ID NO.: 343-345 and CDRH1-H3 and L1-L3 as described in 347-349), and is an engineered variant of an antibody isolated from a patient who has recovered from SARS-CoV-1 infection. Vero E6 cells cultured in DMEM supplemented with 10% FBS (VWR) and 1x penicillin/streptomycin (Thermo Fisher Scientific) were seeded at 20,000 cells/well in white 96-well dishes and attached overnight. Serial 1:4 dilutions of the antibody were combined with 200 pfu of SARS-CoV-2 (isolate USA-WA1/2020, passage 3, passaged in Vero E6 cells) at 37°C in a BSL-3 facility Incubate for 30 minutes. The cell supernatant was removed and the virus-antibody mixture was added to the cells. 24 hours post-infection, cells were fixed with 4% paraformaldehyde for 30 minutes, followed by two PBS (pH 7.4) washes, and permeabilized with 0.25% Triton X-100 in PBS for 30 minutes. After blocking in 5% milk powder/PBS for 30 minutes, cells were incubated with a primary antibody targeting SARS-CoV-2 nucleocapsid protein (Sino Biological, cat. 40143-R001) at a 1:2000 dilution for 1 hour . After washing and incubation for 1 hour with secondary Alexa647-labeled antibody mixed with 1 µg/ml Hoechst33342, the discs were imaged on an automated cell imaging reader (Cytation 5, Biotek) using the software provided by the manufacturer Nucleocapsid-positive cells were counted. Data were processed using Prism software (GraphPad Prism 8.0).

7A-7D show the results of infection neutralization assays using additional antibodies against SARS-CoV-2 pseudo-patterned virus. Monoclonal antibodies isolated from patients who recovered from SARS-CoV-2 infection were expressed recombinantly and tested in neutralization assays against murine leukemia virus (MLV) pseudo-patterned with the SARS-CoV-2 spike protein. Figures 7A and 7B each show four antibodies isolated from patients who recovered from SARS-CoV-1 infection, and comparative antibody S309 (VH amino acid sequence of SEQ ID NO.: 139, VL of SEQ ID NO.: 143 Amino acid sequences; results for CDRH1-H3 and L1-L3) as set forth in SEQ ID NO.: 140-142 and 144-146, respectively. Figure 7C shows the results for three antibodies and S309, and Figure 7D shows the results for two antibodies and S309. Antibody "S2H58" in Figure 7D comprises the VH amino acid sequence set forth in SEQ ID NO.:228 and the VL amino acid sequence set forth in SEQ ID NO.:238. Antibodies were tested at the concentrations indicated on the x-axis.

Figures 8A and 8B show the binding of antibodies to the SARS-CoV-2 spike protein RBD and the SARS-CoV-1 spike protein RBD. Monoclonal antibody systems isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested for RBD binding by ELISA. Figure 8A shows five antibodies isolated from a patient recovered from SARS-CoV-1 infection and one comparative antibody, S309 (VH amino acid sequence of SEQ ID NO.: 139, VL amino acid sequence of SEQ ID NO.: 143 Sequences; binding of CDRH1-H3 and L1-L3) as set forth in SEQ ID NO.: 140-142 and 144-146, respectively. Figure 8B shows the binding of the four antibodies and S309. In each of Figures 8A and 8B, the left panel shows binding to the SARS-CoV-2 RBD, and the right panel shows binding to the SARS-CoV-1 RBD. The boxes to the right of each figure indicate the calculated EC50 values for the indicated antibodies.

9A-9F show the results of infection neutralization assays using antibodies against SARS-CoV-2 pseudo-patterned virus. Monoclonal antibodies isolated from patients who recovered from SARS-CoV-2 infection were expressed recombinantly and tested in neutralization assays against murine leukemia virus (MLV) pseudo-patterned with the SARS-CoV-2 spike protein. Antibodies were tested at the concentrations indicated on the x-axis. Calculated IC50, IC80 and IC90 values (expressed in ng/ml) are shown below the graph in each figure.

Figures 10A-10E show antibodies to the SARS-CoV-2 spike protein RBD and the SARS-CoV-1 spike protein RBD (the SARS-CoV-1 spike protein labeled "SARS RBD" in the lower part of the figure in each figure RBD) combination. Monoclonal antibody systems isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested for RBD binding by ELISA. In each of Figures 10A-10E, the upper panel shows binding to the SARS-CoV-2 RBD, and the lower panel shows binding to the SARS-CoV-1 RBD. Boxes to the right of each figure (if present) show calculated EC50 values for the indicated antibodies.

11A-11D show the results of infection neutralization assays using certain monoclonal antibodies. Antibodies were tested in a neutralization assay against murine leukemia virus (MLV) pseudopatterned with the SARS-CoV-2 spike protein. Figure 11A shows the results for monoclonal antibodies S2X193 and S2X195. Figure 11B shows the results for monoclonal antibodies S2X219 and S2X244. Figure 11C shows the results for monoclonal antibodies S2X246 and S2X256. Figure 1 ID shows the results for the monoclonal antibody S2X278. The x-axis shows the total concentration of antibody. Calculated IC50, IC80 and IC90 values (expressed in ng/ml) are shown in the boxes to the right of each figure.

12A-12D show the results of infection neutralization assays using certain monoclonal antibodies. Antibodies were expressed recombinantly and tested in a neutralization assay against vesicular stomatitis virus (VSV) pseudopatterned with the SARS-CoV-2 spike protein. Figure 12A shows the results of monoclonal antibodies S2X193 and S2X195, and the comparative antibody S2X190. Figure 12B shows the results for the monoclonal antibody S2X219. Figure 12C shows the results for monoclonal antibodies S2X244, S2X246 and S2X256. Figure 12D shows the results for monoclonal antibodies S2X269 and S2X278. Antibodies were tested at the concentrations indicated on the x-axis. Calculated IC50 and IC90 values (expressed in ng/ml) are shown at the bottom of each figure.

Figures 13A and 13B show the ability of certain monoclonal antibodies to inhibit the binding of SARS-CoV-2 RBD to human ACE2. ELISA plates were coated with recombinant human ACE2 in PBS at 2 µg/ml. Serial dilutions of monoclonal antibodies were incubated with SARS-CoV-2 RBD at 20ng/ml (RBD fused to mouse Fc from Sino Biological) for 30 minutes at 37°C and then transferred to ACE2-coated plate and incubate for an additional 20 minutes at room temperature. Eleven serial dilutions were used, starting at 10 µg/ml and diluting at 1:3. Binding of RBD to ACE2 was detected using secondary antibody goat F(ab')2 anti-mouse IgG(H+L) antibody (Southern Biotech) conjugated to alkaline phosphatase, followed by addition of pNPP (Sigma Aldrich N2765- 100 TAB) in bicarbonate buffer and read absorbance at 405 nm.

Figure 13A shows the results for monoclonal antibodies S2X193 and S2X195, and four comparative antibodies. Figure 13B shows the results for monoclonal antibodies S2X219, S2X244, S2X246, S2X256, S2X269 and S2X278. The calculated IC50 values are shown on the right side of the graph of each figure.

Figures 14A-14H show the binding affinity and avidity of certain monoclonal antibodies of the present disclosure to the SARS-CoV-2 RBD, as measured by Octet. Antibodies (as indicated in the lower right of each figure) were loaded onto Protein A needles at 2.7 µg/ml. SARS-CoV-2 RBD was loaded at 6 µg/ml, 1.5 µg/ml or 0.4 µg/ml for 5 minutes. Dissociation was measured for 7 minutes. The vertical dashed line in each figure indicates the start of the dissociation period.

Figure 15 shows monoclonal antibodies S2X219 (first panel) and S2X193, S2X195, S2X244, S2X246, S2X256, S2X269 and S2X278 as measured by Octet, and four comparative antibodies (second panel) with SARS-CoV- 1 Binding affinity and avidity of RBD. The antibody was loaded onto the Protein A needle at 2.7 µg/ml. The SARS-CoV-1 RBD was loaded at 6 µg/ml for 5 minutes. Dissociation was measured for 7 minutes. The vertical dashed line in each figure indicates the start of the dissociation period. In the second set, the order of the curves (top to bottom) corresponds to the antibody scheme (top to bottom) listed to the right of the scheme. By way of illustration, the top surface corresponds to S2X127 and the bottom surface corresponds to S2X278.

Figures 16A-16D show neutralization of SARS-CoV-2 infection by certain monoclonal antibodies as assessed by inhibition of nucleocapsid (NP) expression at 24 hours post infection. FIG. 16A shows the amino acid sequence of VH by monoclonal antibodies S2N22, S2N12, S2N28, S2N25, S2H58-v2 and comparative antibody S309-v2 (SEQ ID NO.:342, VL amino acid sequence of SEQ ID NO.:346) Sequences; neutralization of SARS-CoV-2 infection by CDRH1-H3 and L1-L3) as set forth in SEQ ID NO.: 343-345 and 347-349, respectively. Figure 16B shows the VH amino acid sequence of SEQ ID NO.:399, the VL amino acid sequence of SEQ ID NO.:403 by monoclonal antibodies S2E9, S2E6, S2E13, S2K4, S2E14, S2E7 and S2E12; as respectively CDRH1-H3 and L1-L3 as set forth in SEQ ID NO.: 400, 766, 402 and 404-406), and the neutralization of SARS-CoV-2 infection by comparative antibody S309-v2. Figure 16C shows neutralization of SARS-CoV-2 infection by monoclonal antibodies S2H37, S2H73, S2H40, S2H70 and S2H71, and comparative antibody S309-v2 (with M428L/N434S Fc mutation). Figure 16D shows neutralization of SARS-CoV-2 infection by monoclonal antibodies S2X30, S2H58-v1, S2H66, S2H62 and S2H30, and comparative antibody S309-v2. Calculated IC50 values are shown below each figure.

Figures 17A-17C show the results of infection neutralization assays using certain monoclonal antibodies. Figure 17A shows the results for monoclonal antibodies S2M11 and S2M28. Figure 17B shows the results for the monoclonal antibody S2M16. Figure 17C shows the results for monoclonal antibodies S2M7 and S2L49. Antibodies were tested in a neutralization assay against murine leukemia virus (MLV) pseudopatterned with the SARS-CoV-2 spike protein. The x-axis shows the total concentration of antibody. Calculated IC50, IC80 and IC90 values (expressed in ng/ml) are shown in the boxes below each figure.

Figures 18A-18E show binding of certain monoclonal antibodies to SARS-CoV-2 Spike, SARS-CoV-2 Spike RBD, SARS-CoV-1 Spike, and SARS-CoV-1 Spike RBD . Antibodies isolated from patients recovered from SARS-CoV-2 infection were recombinantly expressed and tested for Spike and Spike RBD binding by ELISA. The boxes to the right of each figure show the calculated EC50 values (expressed in ng/ml).

Figures 19A-19E show the results of infection neutralization assays using certain monoclonal antibodies. Antibodies were tested in a neutralization assay against murine leukemia virus (MLV) pseudopatterned with the SARS-CoV-2 spike protein. Figure 19A shows the results for monoclonal antibodies S2X149 and S2X179. Figure 19B shows the results for the monoclonal antibody S2D65. Figure 19C shows the results for monoclonal antibody S2D97. Figure 19D shows the results for the monoclonal antibody S2D106. Figure 19E shows the results for monoclonal antibody S2H101. The x-axis shows the total concentration of antibody. The calculated IC50, IC80 and IC90 values are shown in the right box of each figure, in the left column of the box.

Figures 20A and 20B show human monoclonal antibody S2X149 and comparative antibody S309-v2 LS (VH amino acid sequence of SEQ ID NO.:342, VL amino acid sequence of SEQ ID NO.:346; as SEQ ID NO.:346, respectively; : CDRH1-H3 and L1-L3 as described in 343-345 and 347-349; expressed as rIgG1 with M428L and N434S Fc mutations) and SARS-CoV-1 spike protein, SARS-CoV-1 spike protein RBD and binding of the SARS-CoV-2 spike protein RBD. Human monoclonal antibodies were expressed recombinantly and tested for binding by ELISA. Figure 20A shows antibody binding to the SARS-CoV-1 spike protein RBD (top panel) and SARS-CoV-1 spike protein (bottom panel). Figure 20B shows antibody binding to the SARS-CoV-2 spike protein RBD (upper panel) and to uncoated control discs (lower panel). The boxes to the right of the figures show the calculated EC50 values.

Figures 21A and 21B show the binding of human monoclonal antibody S2X179 and comparative antibody S2X200 to SARS-CoV-1 Spike, SARS-CoV-1 Spike RBD, and SARS-CoV-2 Spike RBD. Human monoclonal antibodies were expressed recombinantly and tested for binding by ELISA. Figure 21A shows antibody binding to SARS-CoV-1 spike protein RBD (upper panel) and SARS-CoV-1 spike protein (lower panel). Figure 21B shows antibody binding to the SARS-CoV-2 spike protein RBD (upper panel) and to uncoated control discs (lower panel). The box to the right of the top graph in Figure 21B shows the calculated EC50 values for binding to the SARS-CoV-2 RBD.

Figures 22A and 22B show the binding of human monoclonal antibodies S2H101, S2D65 (22A), S2D97 and S2D106 (22B) to the SARS-CoV-2 spike protein RBD. Antibodies were expressed recombinantly and tested for binding by ELISA. The boxes to the right of the figures show the calculated EC50 values.

Figures 23A and 23B show antibody inhibition of human ACE2 binding by SARS-CoV-2 RBD as measured by ELISA. Figure 23A shows the results for the monoclonal antibody S2X149. Figure 24B shows the results for monoclonal antibody S2X179 and comparative antibody S2X200. Calculated IC50 values are shown to the right of each figure.

Figure 24 summarizes the results of quantitative epitope-specific serology studies using monoclonal antibody S309 and other anti-Spike antibodies, as determined by binding competition, cryo-EM and crystallographic data. Underlined antibodies cross-react with SARS-CoV-1.

Figures 25A and 25B show neutralization of SARS-CoV-2 infection by certain monoclonal antibodies. Figure 25A shows the results for the four antibodies of the present disclosure as well as the comparative antibodies S309 N55Q LS and S2X193. The S309 N55Q LS comprises the VH amino acid sequence set forth in SEQ ID NO: 342 and the VL amino acid sequence set forth in SEQ ID NO: 346, and comprises an MLNS modification in the Fc region. Figure 25B shows the results for antibodies S2X129 and S2X132, and four comparative antibodies. Calculated IC50 values are shown in the boxes below each figure. Calculated EC50 and EC90 values are shown at the bottom of each figure.

Figure 26 shows neutralization of SARS-CoV-2 infection by certain monoclonal antibodies using VSV pseudovirus. Data are from a single experiment in triplicate wells with VSV-luc (Spike protein D19) pseudovirus. "LS"=Fc mutation M428L+N434S.

Figure 27 shows the neutralization of infection by live SARS-CoV-2 by certain monoclonal antibodies. Data are from triplicate wells SARS-CoV-2-luc, MOI 0.1, 6h infection.

Figures 28A and 28B show activation of FcyRIIIa (V158 counterpart) (Figure 28A) and FcyRIIa (H131 counterpart) (Figure 28B) by certain antibodies. Data show experiments using CHO target cells expressing the SARS CoV2 S protein.

Figures 29A and 29B show binding of certain antibodies to SARS-CoV-2 RBD and Spike protein (ELISA).

Figures 30A and 30B show binding of certain antibodies against SARS-CoV-2 RBD, SARS-CoV-2 S protein and SARS-CoV-1 RBD.

Figures 31A and 31B show the binding of antibody S2D106 to SARS-CoV-2 RBD in the presence of various concentrations of AAPH (2,2'-azobis(2-carbamidinopropane) dihydrochloride) or after UV irradiation . Both AAPH and UV radiation were used to induce oxidative stress in antibodies. Figure 31A shows the binding of S2D106 to RBD as measured by indirect ELISA. Figure 31B shows binding of S2D106 as measured by sandwich ELISA; x-axis = concentration of RBD.

32A-32C show neutralization of infection (pseudovirions) by S2E12 and its engineered variants (see Table 22 in Example 9 for the VH and VL sequences of the S2E12 antibody). Figures 32A and 32B show results from two replicates of the same experiment. Figure 32C shows the results of a third experiment using S2E12 and its other variants.

Figures 33A and 33B show binding of certain antibodies to SARS-CoV-2 RBD as measured by indirect ELISA. Figure 33A shows the results for eight antibodies. Figure 33B shows the mean of results from double replicate experiments of six antibodies.

Figures 34A and 34B show the binding of certain antibodies to SARS-CoV-2 RBD as measured by sandwich ELISA. Figure 34A shows the results for eight antibodies. Figure 34B shows the mean of results from double replicate experiments of six antibodies.

Figure 35 shows neutralization of infection by five antibodies using live SARS-CoV-2 virus. The curve labeled "S2E12-11" was generated using the antibody present in the supernatant of CHO cells transformed to express the S2E12 antibody. A curve labeled "S2E12 wt" was generated using purified antibody produced in transformed HEK cells.

Figure 36 shows the binding of certain antibodies to the SARS-CoV-2 spike protein expressed on the surface of CHO cells, as measured by flow cytometry. Calculated EC50 values for each antibody are shown in the legend to the right of each antibody name. The curve labeled "S2E12-11" was generated using the antibody present in the supernatant of CHO cells transformed to express the S2E12 antibody. A curve labeled "S2E12" was generated using purified antibody produced in transformed HEK cells.

Figures 37A and 37B show neutralization of infection by certain monoclonal antibodies using pseudovirions. Figures 37A and 37B show results from two replicates of the same experiment.

Figures 38A and 38B show binding of certain antibodies to the SARS-CoV-2 RBD. Also shown is the binding of the comparative antibody S309-14 (S309 with the VH W105F mutation, with an affinity for RBD similar to that of S309). Figure 38A shows binding as measured by indirect ELISA. Figure 38B shows binding as measured by sandwich ELISA. Each of Figures 38A and 38B shows the mean of results from double replicate experiments.

Figures 39A and 39B show the characteristics of certain engineered S2E12 antibodies compared to the parental monoclonal antibody S2E12 (S2E12 values, indicated as "WT" on the y-axis). Comparative data were generated using the analyses listed in the legend to the right of each figure.

Figure 40 shows the characteristics of certain engineered S2D106 antibodies compared to the parental monoclonal antibody S2D106 (S2D106 values, indicated as "WT" on the y-axis). Comparative data were generated using the analyses listed in the legend to the right of each figure.

Figure 41 shows the expression (immunofluorescence) of DC-SIGN/L-SIGN, DC-SIGN and ACE2 transgenic genes in HEK293T cells engineered to overexpress the indicated proteins. See Example 14.

Figure 42 shows the level of VSV pseudovirus infection in wild-type HEK293T cells and HEK293T cells engineered to overexpress DC-SIGN, L-SIGN or ACE2. The pseudovirus expresses a recombinant SARS-CoV-2 spike protein with a luciferase reporter. See Example 14.

Figure 43 shows infection of monoclonal antibody S309 by VSV pseudovirus in HEK293T cells engineered to overexpress DC-SIGN, L-SIGN or ACE2 (VH of SEQ ID NO.:139, SEQ ID NO.:143 the neutralization of VL). In this example, antibody S309 includes the M428L and N434S Fc mutations. See Example 14.

Figure 44 shows the level of infection by live SARS-CoV-2 in wild-type HEK293T cells and HEK293T cells engineered to overexpress DC-SIGN, L-SIGN or ACE2. Infection was determined using recombinant S protein with a luciferase reporter. See Example 14.

Figure 45 shows infection by live SARS-CoV-2 in HEK293T cells engineered to overexpress DC-SIGN, L-SIGN or ACE2, monoclonal antibody S309 (VH of SEQ ID NO.: 139, SEQ ID NO.: 139) Neutralization of VL) of ID NO.: 143. In this example, antibody S309 includes the M428L and N434S Fc mutations. See Example 14.

Figure 46 shows the expression (immunofluorescence) of DC-SIGN/L-SIGN, DC-SIGN, SIGLECl and ACE2 transgenic genes in HEK293T cells engineered to overexpress the indicated proteins. See Example 14.

Figure 47 shows the level of infection by live SARS-CoV-2 in wild-type HEK293T cells and HEK293T cells engineered to overexpress DC-SIGN, L-SIGN, SIGLEC-1 or ACE2. Infection was determined using recombinant S protein with a luciferase reporter. See Example 14.

Figure 48 shows monoclonal antibody S309 (SEQ ID NO.: 139) of infection by live SARS-CoV-2 in HEK293T cells engineered to overexpress DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 Neutralization of VH of SEQ ID NO.: 143 of VL). In this example, antibody S309 includes the M428L and N434S Fc mutations. See Example 14.

Figure 49 shows the monoclonal antibody S2E12-LS (SEQ ID NO. : VH of 399, VL of SEQ ID NO.: 403, neutralization with M428L/N434S Fc mutation). In this example, antibody S2E12 includes the M428L and N434S Fc mutations. See Example 14.

Figures 50A and 50B show expression analysis of receptor proteins including CD209 (DC-SIGN) and SIGLEC proteins in several cell types. The size of the dots is related to the percentage of cells of the indicated type expressing the protein, and the intensity of the dot shading is related to the level of protein expression. See Example 14.

Figure 51 shows live SARS-CoV-2 by expression of N-luciferase in HEK293T cells ("parent") or in HEK293T cells stably expressing DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 infection. Data represent experiments testing SARS-CoV-2 at three multiples of infection (MOI). See Example 14.

Figure 52 shows infection by SARS-CoV-2 pseudo-patterned VSV in HEK293T cells, HeLa cells and MRC5 cells transiently transduced with lentivirus to express DC-SIGN, L-SIGN, SIGLEC-1 or ACE2. Uninfected cells are shown as negative controls. See Example 14.

Figure 53 shows neutralization of infection by S2E12. A panel of 7 cell lines (HeLa, 293T (wt), Vero E6, Huh7, 293T ACE2, MRC 5-ACE2-TMPRSS2, A549-ACE2-TMPRSS2 clone 5, A549-ACE2-TMPRSS2 clone 10) were grown in the presence of S2E12 Infection by SARS-CoV-2-Nluc. Luciferase signal was quantified 24 h after infection.

Figure 54 shows neutralization of infection by S2E12. A set of 7 cell lines (HeLa, 293T (wt), Vero E6, Huh7, 293T ACE2, MRC 5-ACE2-TMPRSS2, A549-ACE2-TMPRSS2 clone 5, A549-ACE2-TMPRSS2 clone 10) were grown in S2E12-LS Infection with VSV pseudopatterned with the SARS-CoV-2 spike protein in the presence of SARS-CoV-2. Luciferase signal was quantified 24 h after infection.

Figure 55 shows the binding of purified fluorescently labeled SARS-CoV-2 spike protein to each of the seven cell lines as quantified by flow cytometry. HeLa and 239T WT cells already had the lowest MFI, followed by Huh7 and VeroE6 cells. 293T ACE2 cells (highest), MRC 5-ACE2-TMPRSS2 (third highest), A549-ACE2-TMPRSS2 clone 5 (fourth highest) and A549-ACE2-TMPRSS2 clone 10 (second highest) had higher MFIs.

Figures 56A and 56B show that both S309 (VH SEQ ID NO.: 139; VL SEQ ID NO.: 143) or the combination of S309 and S2E12-LS provide robust in vivo protection against SARS-CoV-2 challenge. Syrian hamsters were injected with the indicated amounts of mAb 48 hours prior to intranasal challenge with SARS-CoV-2. Figure 56A top column shows quantification of viral RNA in lungs 4 days post infection. Figure 56A middle column shows quantification of replicating virus in lung homogenates harvested 4 days post infection using TCID50 analysis. The bottom column of Figure 56A shows histological scores of lung tissue assessed 4 days post infection. Figure 56B shows that mAb concentrations measured in serum prior to infection (day 0) were inversely proportional to viral RNA load in the lungs 4 days post infection. See Example 14.

Figure 57 shows infection by VSV-SARS-CoV-2 pseudovirus of HEK293T cells transfected to overexpress ACE2 or one of a panel of selected lectin and receptor candidates.

Figure 58 shows photomicrographs of stable HEK293T cell lines overexpressing DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 transfected with authentic SARS-CoV-2 (MOI of 0.1) followed by fixation and immunostained for SARS-CoV-2 nucleoprotein (red) for 24 hours.

Figure 59 shows quantification of luciferase levels in stable HEK293T cell lines overexpressing DC-SIGN, L-SIGN, SIGLEC-1 or ACE2, as 24 hours after infection with SARS-CoV-2-Nluc Measure.

Figure 60 shows stabilization of overexpressed DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 following incubation with various concentrations of anti-SIGLEC1 monoclonal antibody (clone 7-239) and infection with SARS-CoV-2-Nluc Quantification of luciferase levels in HEK293T cell line.

Figure 61 shows infection by VSV-SARS-CoV-2 pseudovirus of cells transiently transduced to overexpress DC-SIGN, L-SIGN, SIGLEC-1 or ACE2. Results are shown for HEK293T cells (left panel), HeLa cells (middle panel) and MRC5 cells (right panel).

Figure 62 shows infection of stable HEK293T cell lines overexpressing DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 following treatment with ACE2 siRNA followed by infection with VSV-SARS-CoV-2 pseudovirus.

Figure 63 shows stable HEK293T overexpressing DC-SIGN, L-SIGN, SIGLEC-1 or ACE2 following treatment with different concentrations of anti-ACE2 antibodies (polyclonal serum) followed by infection with VSV-SARS-CoV-2 pseudovirus Infection of cell lines.

Figure 64 shows the distribution and representation of ACE2, DC-SIGN (CD209), L-SIGN (CLEC4M) and SIGLEC1 in the Human Lung Cell Atlas.

Figure 65 shows the analysis of the major cell types with detectable SARS-CoV-2 gene bodies in bronchoalveolar lavage fluid or sputum from severe COVID-19 patients. Single-cell gene expression profiles are shown as t-SNE (t-distributed stochastic neighborhood embedding) curves, stained by cell type and sized by viral load.

Figure 66 shows analysis of major cell types with detectable SARS-CoV-2 gene bodies in bronchoalveolar lavage fluid or sputum from severe COVID-19 patients. The cumulative fraction of cells (y-axis) for each of the indicated cell types is shown with viral RNA/cell detected to the corresponding logCPM (log(counts/million); x-axis).

Figure 67 shows a heatmap matrix with cell counts for the receptor genes shown on the x-axis and transcripts detected for the SARS-CoV-2+ cell type shown on the y-axis. Total n=3,085 cells from eight individuals. See Ren, X. et al., COVID-19 immune features revealed by a large-scale single cell transcriptome atlas. Cell, doi: 10.1016/j.cell.2021.01.053 (2021).

Figure 68 shows the correlation of receptor transcript counts (y-axis of each curve) and SARS-CoV-2 RNA counts (x-axis of each curve) in macrophages and in secretory cells. Correlations are based on pre-log-transformed counts from Ren et al.

The right side of Figure 69 shows the results of counter-infection with VSV-SARS-CoV-2. A schematic diagram of the anti-infection process is shown in the left panel. HeLa cells transduced with DC-SIGN, L-SIGN or SIGLEC1 were incubated with VSV-SARS-CoV-2, washed extensively and co-cultured with Vero-E6-TMPRSS2 sensitive target cells. Results in the presence or absence of target cells are shown in the right panel.

Figure 70 shows the results of counterinfection with VSV-SARS-CoV-2 viral uptake in the presence or absence of anti-SIGLEC1 blocking antibodies.

Figure 71 shows neutralization of SARS-CoV-2 infection of Vero-E6 cells by antibodies S309, S2E12-LS and S2X33. S2E12-LS comprises the VH sequence of SEQ ID NO:399 and the VL sequence of SEQ ID NO:403 and M428L/N434S in Fc.

Figure 72 shows neutralization of SARS-CoV-2 infection of Vero-E6-TMPRSS2 cells by antibodies S309, S2E12-LS and S2X33.

Figure 73 shows quantification of the binding of purified fluorescently labeled SARS-CoV-2 spike protein or RBD to the indicated cell lines as measured by flow cytometry. "A" indicates a cell line overexpressing ACE2; "T" indicates a cell line overexpressing TMPRSS2.

Figure 74 shows quantification of cellular ACE2 and TMPRSS2 transcripts in the indicated cell lines as measured by RT-qPCR. "A" indicates a cell line overexpressing ACE2; "T" indicates a cell line overexpressing TMPRSS2.

Figure 75 shows neutralization of SARS-CoV-2-Nluc infection by antibodies S309, S2E12-LS or S2X333. Each of the seven indicated cell lines was tested. Luciferase signal was quantified 24 hours after infection.

Figure 76 shows neutralization of VSV-SARS-CoV-2 pseudovirus infection by antibodies S309, S2E12-LS or S2X333. Each of the seven indicated cell lines was tested. Luciferase signal was quantified 24 hours after infection.

Figure 77 shows expression of SARS-CoV-2 S protein (CHO) on the plasma membrane in the absence (upper panel) or presence (lower panel) of 5 µg/ml of antibody S2E12-LS, as measured by immunofluorescence -S) Cell-cell fusion of CHO cells. Nuclei were stained with Hoechst dye; cytoplasm was stained with CellTracker green.

Figure 78 shows CHO-S cell-cell fusion mediated by different Spike-specific antibodies. Fusion was quantified using a Cytation 5 Imager (BioTek) and an object detection protocol that detected nuclei as objects and measured their size. The area of objects in fused cells is divided by the total area of all objects multiplied by 100 to obtain the percentage of fused cells.

Figure 79 shows inhibition of S2E12-LS-induced cell-cell fusion of CHO-S cells by 15 μg/ml of the indicated antibodies.

Figure 80 shows S2E12-LS-induced unidirectional fusion (also known as anti-fusion) of S-positive CHO-S cells with fluorescently labeled S-negative CHO cells in the absence of ACE2. Nuclei were stained with Hoechst dye; cytoplasm was stained with CellTracker green.

Figure 81 shows infection of a stable HEK293T cell line overexpressing ACE2 neutralized by reliable SARS-CoV-2 preincubation with the indicated antibodies. SARS-CoV-2 nucleoprotein infection was measured by immunostaining at 24 hours.

Figure 82 shows infection of a stable HEK293T cell line overexpressing SIGLEC1 neutralized by reliable SARS-CoV-2 preincubation with the indicated antibodies. SARS-CoV-2 nucleoprotein infection was measured by immunostaining at 24 hours.

Figure 83 shows infection by robust SARS-CoV-2 neutralization of DC-SIGN overexpressing stable HEK293T cell line preincubated with the indicated antibodies. SARS-CoV-2 nucleoprotein infection was measured by immunostaining at 24 hours.

Figure 84 shows the neutralization of infection of a stable HEK293T cell line overexpressing L-SIGN by reliable SARS-CoV-2 preincubation with the indicated antibodies. SARS-CoV-2 nucleoprotein infection was measured by immunostaining at 24 hours.

Figure 85 shows an overview of the mechanism of action of different classes of Spike-specific antibodies. "Inhibition of fusion" refers to inhibition of antibody-mediated fusion between CHO-S cells and ACE2+ Vero-E6 cells. Assessment of effector function is based on antibody-dependent activation of human FcγRs, as measured using a bioluminescent reporter assay. RBM Ia-IIa antibodies include S2E12, S2X259, S2X58, S2D106, Ly-CoV016, CT-P59 and REGN10933. RBM Ib antibodies include Ly-CoV555, REGN10987 and S2M11. NTD antibodies include S2X333. Dry helix antibodies include S2P6.

Figure 86 shows analysis of binding of antibodies targeting DC/L-SIGN, DC-SIGN, SIGLEC1 or ACE2 on HEK293T cells stably overexpressing the corresponding adhesion receptors, as measured by flow cytometry .

Figure 87 shows analysis of binding of antibodies targeting DC/L-SIGN, DC-SIGN, SIGLECl or ACE2 on HEK293T cells stably overexpressing the corresponding adhesion receptors, as measured by immunofluorescence.

Figure 88 shows that the indicated adhesion receptor HEK293T cells were stably overexpressed by VSV-SARS-CoV-2 pseudopatterned with wild-type Spike protein (grey bars) or by spikes carrying mutations of the B1.1.7 lineage Protein (red bars) pseudo-patterned infection with VSV-SARS-CoV-2. Luminescence was analyzed one day after infection.

Figure 89 shows neutralization of SARS-CoV-2 infection of Vero-E6 or Vero-E6-TMPRSS2 cells by 10 μg/ml S309, S2E12-v2 and S2X333. Cells were infected with SARS-CoV-2 (isolate USA-WA1/2020) at MOI 0.01 in the presence of the indicated antibodies. Cells were fixed 24 h after infection and immunostained for viral nucleocapsid proteins.

Figure 90 shows quantification of the binding of purified fluorescently labeled SARS-CoV-2 spike protein (left panel) or RBD (right panel) to the indicated cell lines as measured by flow cytometry.

Figure 91 shows quantification of the binding of purified fluorescently labeled SARS-CoV-2 spike protein (left panel) or RBD (right panel) to the indicated cell lines as measured by flow cytometry.

Figure 92 shows analysis of the protective effect of antibody S309 (left panel) or the combination of antibodies S309 and S2E12-v2 (right panel) against SARS-CoV-2 challenge in Syrian hamsters. The upper panel shows the quantification of viral RNA in the lungs four days post infection. The lower panel shows the quantification of replicating virus in lung homogenates harvested four days post infection using TCID50 analysis.

Figure 93 shows analysis of the protective effect of antibody S309 (left panel) or the combination of antibodies S309 and S2E12-LS (right panel) against SARS-CoV-2 challenge in Syrian hamsters. The upper panel shows the histopathological score of lung tissue assessed four days post-infection. The graph below shows the correlation between the level of SARS-CoV-2 viral RNA measured in the lung (y-axis) based on the level of serum antibodies measured at the time of infection (x-axis) and the fourth day post-infection Sexual Efficacy Chart. Dotted lines represent EC50 and EC90 for virus reduction. The EC90 of S309 alone is 9 µg/ml; the EC90 of S309+S2E12-v2 is 11 µg/ml.

Figure 94 shows binding of immune complexes to hamster splenocytes. Alexa-488 fluorescent immune complexes (IC) (0-200 nM range) were titrated and incubated with total untreated hamster splenocytes. Binding was uncovered with a cytometer when dead/apoptotic cells were excluded and gated on true monocyte population entities. The left panel shows the fluorescence intensities associated with hamster cells made intradermally with hamster or human Fc antibodies (human S309 is shown in green; GH-S309 is shown in dark grey; GH-S309-N297A is shown in blue). A single repetition of two is shown. The right panel shows the relative Alexa-488 mean fluorescence intensity of replicates measured over the entire mononucleate population.

Figure 95 shows an analysis of the role of host effector functions in SARS-CoV-2 challenge. Syrian hamsters were injected with the indicated amounts (mg/kg) of hamster IgG2a S309, wt or Fc silenced (S309-N297A). The upper panel shows the quantification of viral RNA in the lungs 4 days post-infection. The middle panel shows the quantification of replicating virus in the lungs 4 days post-infection. Lower panels show histopathological scores in the lungs 4 days post-infection. Control animals (white symbols) were injected with 4 mg/kg of irrelevant control isotype antibody. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 vs. control animals using the Mann-Whitney test.

Figure 96 shows inhibition of infection by SARS-CoV-2-Nluc in HeLa cells stably expressing DC-SIGN in the presence of the indicated antibodies. Cells were infected at an MOI of 0.04. Infections were analyzed by quantifying the luminescence signal 24 hours after infection.

Figure 97 shows neutralization of SARS-CoV-2 infection of HEK293T cells stably expressing ACE2 (upper panel) or DC-SIGN (lower panel) in the presence of the indicated antibodies. Cells were infected at an MOI of 0.02. Cells were fixed 24 h after infection, immunostained for viral nucleocapsid protein and positive cells were quantified.

Figure 98 shows neutralization of SARS-CoV-2 infection of HEK293T cells stably expressing SIGLEC1 (upper panel) or L-SIGN (lower panel) in the presence of the indicated antibodies. Cells were infected at an MOI of 0.02. Cells were fixed 24 h after infection, immunostained for viral nucleocapsid protein and positive cells were quantified.

Figure 99 shows the concentration profile of the S2E12 engineered variant 409_11_4_v2 comprising the LS mutation in the Fc in female non-human primates over 64 days.

Figure 100 shows 409_11_4_v2-LS pharmacokinetic values from non-human primate studies.

Claims (107)

An antibody or antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a CDRH1, a CDRH2 and a CDRH3, and the The light chain variable domain (VL) comprises a CDRL1, a CDRL2 and a CDRL3, wherein: (i) the CDRH1 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NOs.: 400, 23, 33, 43, 53, 63, 75, 85, 97, 107, 120, 130, 140, 147, 160, 170, 174, 183, 190, 199, 209, 219, 229, 241, 255, 265, 275, 285, 299, 313, 323, 333, 370, 380, 390, 410, 420, 430, 435, 445, 455, 465, 475, 485, 495, 505, 515, 525, 535, 545, 555, 565, 575, 585, 595, 605, 615, 631 and 693, or a combination thereof Sequence variants with one, two or three amino acid substitutions, one or more of which is optionally a conservative substitution and/or a substitution to a germline encoded amino acid; (ii) the CDRH2 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NOs.: 401, 24, 34, 44, 54, 64, 76, 86, 98, 108, 121, 131, 141, 148, 151, 161, 171, 184, 200, 210, 220, 230, 242, 256, 266, 276, 286, 300, 314, 324, 334, 352, 360, 362, 364, 366, 371, 381, 391, 411, 421, 431, 436, 446, 456, 466, 476, 486, 496, 506, 516, 526, 536, 546, 556, 566, 576, 586, 596, 606, 616, 625, 632, 635, 637, 639, 641, 643, 645, 647, 649, 651, 653, 655, 657, 659, 661, 663, 665, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685 and 694, or a sequence variant thereof comprising one, two or three amino acid substitutions, one or more of which are optionally a conservative substitution and/or a Substitution of one of the germline encoded amino acids; (iii) the CDRH3 comprises or consists of an amino acid sequence according to any one of the following: SEQ ID NOs.: 766, 25, 35, 45, 55, 65, 77, 87, 99, 109, 122, 132, 142, 149, 162, 164, 165, 172, 176, 177, 179, 180, 185, 187, 188, 201, 211, 221, 231, 243, 257, 267, 277, 287, 301, 315, 325, 335, 354, 372, 382, 392, 412, 422, 432, 437, 447, 457, 467, 477, 487, 497, 507, 517, 527, 537, 547, 557, 567, 577, 587, 597, 607, 617, 627, 633, 695, 751, 753, 755, 757, 760, 763, 765 and 402, or a sequence variant thereof comprising one, two or three amino acid substitutions, the one or more of the substitutions is optionally a conservative substitution and/or a substitution to a germline encoded amino acid; (iv) the CDRL1 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NOs.: 404, 27, 37, 47, 57, 67, 79, 89, 101, 111, 124, 134, 144, 152, 155, 156, 158, 159, 166, 181, 192, 203, 213, 223, 233, 245, 259, 269, 279, 289, 303, 317, 327, 337, 356, 374, 384, 394, 414, 424, 439, 449, 459, 469, 479, 489, 499, 509, 519, 529, 539, 549, 559, 569, 579, 589, 599, 609, 619, 687 and 697, or a sequence variant comprising one, two or three amino acid substitutions, one or more of which are optionally a conserved substitution and/or a change to a germline encoded amino acid a replacement; (v) the CDRL2 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NOs.: 405, 28, 38, 48, 58, 68, 80, 90, 102, 112, 125, 135, 145, 153, 167, 182, 193, 204, 214, 224, 234, 246, 260, 270, 280, 290, 304, 318, 328, 338, 375, 385, 395, 415, 425, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 688, and 698, or a combination of one, two, or three Sequence variants of amino acid substitutions, one or more of which are optionally a conservative substitution and/or a substitution to a germline-encoded amino acid; and/or (vi) the CDRL3 comprises or consists of an amino acid sequence according to any of the following: SEQ ID NOs.: 406, 29, 39, 49, 59, 69, 81, 91, 103, 113, 126, 136, 146, 169, 195, 197, 205, 215, 225, 235, 247, 261, 271, 281, 291, 305, 319, 329, 339, 358, 376, 386, 396, 416, 426, 441, 451, 461, 471, 481, 491, 501, 511, 521, 531, 541, 551, 561, 571, 581, 591, 601, 611, 621, 689, 699, 745, and 747, or one of them including one, Sequence variants of two or three amino acid substitutions, one or more of which is optionally a conservative substitution and/or a substitution to a germline encoded amino acid, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. The antibody or antigen-binding fragment of claim 1, which is capable of neutralizing a SARS-CoV-2 infection in an in vitro infection model and/or an in vivo animal infection model and/or a human. The antibody or antigen-binding fragment of any one of claims 1 to 2, comprising the following CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences: (i) are SEQ ID NOs.: 400, 401, 766 and 404-406, respectively; (ii) SEQ ID NOs.: 400-402 and 404-406, respectively; (iii) SEQ ID NOs.: 43-45 and 47-49, respectively; (iv) are SEQ ID NOs.: 53-55 and 57-59, respectively; (v) are SEQ ID NOs.: 63-65 and 67-69, respectively; (vi) are SEQ ID NOs.: 75-77 and 79-81, respectively; (vii) are respectively SEQ ID NOs.: 85-87 and 89-91; (viii) are SEQ ID NOs.: 97-99 and 101-103, respectively; (ix) are respectively SEQ ID NOs.: 107-109 and 111-113; (x) are respectively SEQ ID NOs.: 120-122 and 124-126; (xi) are respectively SEQ ID NOs.: 130-132 and 134-136; (xii) are respectively SEQ ID NOs.: 23 or 147, any one of 24, 148 or 151, 25 or 149, any one of 27, 152, 155, 156, 158 or 159, 28 or 153, and 29; (xiii) is any of SEQ ID NOs.: 43 or 160, 44 or 161, 45, 162, 164 or 165, 47 or 166, 48 or 167, and 49 or 169, respectively; (xiv) are SEQ ID NOs.: any one of 130, 170 or 174, 130, 131, 132, 134 or 181, 135 or 182, and 136, respectively; (xv) are SEQ ID NOs.: any one of 53, 183 or 190, 54 or 184, any one of 55, 185, 187 or 188, any one of 57 or 192, 58 or 193, respectively , and any of 59, 195 or 197; (xvi) are respectively SEQ ID NOs.: 199-201 and 203-205; (xvii) are respectively SEQ ID NOs.: 209-211 and 213-215; (xviii) are SEQ ID NOs.: 219-221 and 223-225, respectively; (xix) are respectively SEQ ID NOs.: 229-231 and 233-235; (xx) are SEQ ID NOs.: 241-243 and 245-247, respectively; (xxi) are respectively SEQ ID NOs.: 255-257 and 259-261; (xxii) are SEQ ID NOs.: 265-267 and 269-271, respectively; (xxiii) are SEQ ID NOs.: 275-277 and 279-281, respectively; (xxiv) are SEQ ID NOs.: 285-287 and 289-291, respectively; (xxv) are respectively SEQ ID NOs.: 299-301 and 303-305; (xxvi) are SEQ ID NOs.: 313-315 and 317-319, respectively; (xxvii) are SEQ ID NOs.: 323-325 and 327-329, respectively; (xxviii) are SEQ ID NOs.: 333-335 and 337-339, respectively; (xxix) are SEQ ID NOs.: 229, 230 or 352, 231 or 354, and 233 or 356, 234, and 235 or 358, respectively; (xxx) are any of SEQ ID NOs.: 313, 314, 360, 362, 364 or 366, 315 and 317-319, respectively; (xxxi) are SEQ ID NOs.: 370-372 and 374-376, respectively; (xxxii) are SEQ ID NOs.: 380-382 and 384-386, respectively; (xxxiii) are SEQ ID NOs.: 390-392 and 394-396, respectively; (xxxiv) are respectively SEQ ID NOs.: 23-25 and 27-29; (xxxv) are respectively SEQ ID NOs.: 410-412 and 414-416; (xxxvi) are SEQ ID NOs.: 420-422 and 424-426, respectively; (xxxvii) are respectively SEQ ID NOs.: 435-437 and 439-441; (xxxviii) are SEQ ID NOs.: 445-447 and 449-451, respectively; (xxxix) are SEQ ID NOs.: 455-457 and 459-461, respectively; (xxxx) are SEQ ID NOs.: 465-467 and 469-471, respectively; (xxxxi) are respectively SEQ ID NOs.: 475-477 and 479-481; (xxxxii) are SEQ ID NOs.: 485-487 and 489-491, respectively; (xxxxiii) are SEQ ID NOs.: 494-497 and 499-501, respectively; (xxxxiv) are SEQ ID NOs.: 505-507 and 509-511, respectively; (xxxxv) are SEQ ID NOs.: 515-517 and 519-521, respectively; (xxxxvi) are respectively SEQ ID NOs.: 525-527 and 529-531; (xxxxvii) are respectively SEQ ID NOs.: 535-537 and 539-541; (xxxxviii) are SEQ ID NOs.: 545-547 and 549-551, respectively; (xxxixix) are SEQ ID NOs.: 555-557 and 559-561, respectively; (xxxxx) are SEQ ID NOs.: 565-567 and 569-571, respectively; (xxxxx) are respectively SEQ ID NOs.: 575-577 and 579-581; (xxxxxii) are SEQ ID NOs.: 585, 586 or 625, 587 or 627, and 589-591, respectively; (xxxxxiii) are SEQ ID NOs.: 595-597 and 599-601, respectively; (xxxxxiv) are respectively SEQ ID NOs.: 605-607 and 609-611; (xxxxxv) are respectively SEQ ID NOs.: 615-617 and 619-621; (xxxxxvi) are SEQ ID NOs.: 631, 632 or 635 or 637 or 639 or 641 or 643 or 645 or 647 or 649 or 651 or 653 or 655 or 657 or 659 or 661 or 663 or 665 or 667 or 669 or 671 or 673 or 675 or 677 or 679 or 681 or 683 or 685, 633 and 697-699; (xxxxxvii) are SEQ ID NOs.: 693-695 and 697-699, respectively; (xxxxxviii) are SEQ ID NOs.: 400, 401, and any one of 751, 753, 755, 757, or 760, and any one of 404, 405, and 745 or 747, respectively; (xxxxxxix) are SEQ ID NOs.: 585, 586, and 762 or 764, and 589-591, respectively; (xxxxxxx) are SEQ ID NOs.: 33-35 and 37-39, respectively; or (xxxxxxx) are respectively SEQ ID NOs.: 400; 401; 766; 404; 405 or a variant of SEQ ID NO.: 405 comprising one, two or three amino acid substitutions, wherein the one, two or and 406, each of the three amino acid substitutions is optionally a conserved amino acid substitution; An antibody or antigen-binding fragment thereof comprising CDRH1, CDRH2 and CDRH3 of the VH amino acid sequence set forth in SEQ ID NO.:399, and CDRL1 of the VL amino acid sequence set forth in SEQ ID NO.:738 ; CDRL2 or a variant of the CDRL2 comprising one, two or three amino acid substitutions, wherein each of the one, two or three amino acid substitutions is optionally a conserved amino acid and CDRL3, wherein the CDRs are according to IMGT, And wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising complementarity determining regions (CDR) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in: (a) SEQ ID NOs, respectively .: 400, 401, 766, 404, 405 and 406; (b) respectively SEQ ID NOs.: 400, 401, 769, 404, 405 and 406; (c) respectively SEQ ID NOs.: 400, 401, 770, 404, 405 and 406; (d) are SEQ ID NOs.: 400, 401, 771, 404, 405 and 406, respectively; (e) are SEQ ID NOs.: 400, 401, 772, 404, 405 and 406; (f) are SEQ ID NOs.: 400, 401, 773, 404, 405 and 406, respectively; (g) are SEQ ID NOs.: 400, 401, 766, 404, 405 and 745, respectively; (h) are respectively are SEQ ID NOs.: 400, 401, 769, 404, 405 and 745; (i) are SEQ ID NOs.: 400, 401, 770, 404, 405 and 745, respectively; (j) are SEQ ID NOs.: 400, 401, 771, 404, 405 and 745; (k) are respectively SEQ ID NOs.: 400, 401, 772, 404, 405 and 745; (l) are respectively SEQ ID NOs.: 400, 401, 773, 405, 405 and 745; (m) are SEQ ID NOs.: 400, 401, 766, 404, 405 and 747, respectively; (n) are SEQ ID NOs.: 400, 401, 769, 404, 405 and 747, respectively; (o) SEQ ID NOs.: 400, 401, 770, 404, 405, and 747, respectively; (p) SEQ ID NOs.: 400, 401, 771, 404, 405, and 747, respectively; (q) SEQ ID NOs.: 400, 401, 771, 404, 405, and 747, respectively ID NOs.: 400, 401, 772, 404, 405 and 747; or (r) are SEQ ID NOs.: 400, 401, 773, 404, 405 and 747, respectively, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. The antibody or antigen-binding fragment thereof of claim 5, comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a CDRH1, a CDRH2 and a CDRH3, and the light chain variable domain (VL) comprises a CDRL1, a CDRL2 and a CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in the following: (a) respectively SEQ ID NOs.: 400, 401, 766, 404, 405 and 406. The antibody or antigen-binding fragment of any one of claims 4 to 6, comprising the amino acid sequence set forth in: (a) SEQ ID NOs.: 400, 401, 402, 404, 405, and 406; ( b) SEQ ID NOs.: 400, 401, 751, 404, 405 and 406; (c) SEQ ID NOs.: 400, 401, 753, 404, 405 and 406; (d) SEQ ID NOs.: 400, 401 , 755, 404, 405 and 406; (e) SEQ ID NOs.: 400, 401, 757, 404, 405 and 406; (f) SEQ ID NOs.: 400, 401, 760, 404, 405 and 406; ( g) SEQ ID NOs.: 400, 401, 402, 404, 405 and 745; (h) SEQ ID NOs.: 400, 401, 751, 404, 405 and 745; (i) SEQ ID NOs.: 400, 401 , 753, 404, 405 and 745; (j) SEQ ID NOs.: 400, 401, 755, 404, 405 and 745; (k) SEQ ID NOs.: 400, 401, 757, 404, 405 and 745; ( l) SEQ ID NOs.: 400, 401, 760, 404, 405 and 745; (m) SEQ ID NOs.: 400, 401, 402, 404, 405 and 747; (n) SEQ ID NOs.: 400, 401 , 751, 404, 405 and 747; (o) SEQ ID NOs.: 400, 401, 753, 404, 405 and 747; (p) SEQ ID NOs.: 400, 401, 755, 404, 405 and 747; ( q) SEQ ID NOs.: 400, 401, 757, 404, 405 and 747; or (r) SEQ ID NOs.: 400, 401, 760, 404, 405 and 747. The antibody or antigen-binding fragment of any one of claims 4 to 7, comprising the amino acid sequence set forth in SEQ ID NO.: 400, the amino acid sequence set forth in SEQ ID NO.: 401 in VH Sequence and amino acid sequence set forth in SEQ ID NO.:402, and in VL comprising the amino acid sequence set forth in SEQ ID NO.:404, the amino acid sequence set forth in SEQ ID NO.:405 Sequence and amino acid sequence set forth in SEQ ID NO.:406. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising complementarity determining regions (CDR) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in: SEQ ID NOs.:525, respectively , 526, 527, 529, 530 and 531, And wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising complementarity determining regions (CDR) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2, and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences set forth in: SEQ ID NOs.: 585, respectively ; 586 or 625; 587 or 627; 589; 590; and 591, And wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising complementarity determining regions (CDR) H1, CDRH2 and CDRH3, and the light chain variable domain (VL) comprises CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in: SEQ ID NOs.: 229, respectively , 230, 231, 233, 234 and 235, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. The antibody or antigen-binding fragment of any one of claims 1 to 11, wherein: (i) the VH comprises at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical monoamino acid sequences or consist of: SEQ ID NOs.: 399, 22, 32, 42 , 52, 62, 72, 74, 84, 96, 106, 119, 129, 139, 150, 163, 173, 175, 178, 186, 189, 191, 198, 208, 218, 228, 240, 254, 264 , 274, 284, 298, 312, 322, 332, 350, 351, 353, 359, 361, 363, 365, 367, 368, 369, 379, 389, 409, 419, 429, 434, 444, 454, 464 , 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 626, 628, 630, 634, 636, 638, 640, 642, 644 , 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 692, 740, 741, 742, 743 , 748, 749, 750, 752, 754, 756, 758, 759, 761, 762, and 764, wherein the change is optionally limited to one or more framework regions and/or the change comprises one or more pairs of a germline encoding amino acid substitution; and/or (ii) the VL comprises at least 85% (eg, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical monoamino acid sequences or consist of: SEQ ID NO.: 738, 26, 36, 46 , 56, 66, 78, 88, 94, 100, 110, 123, 133, 143, 154, 157, 168, 194, 196, 202, 212, 222, 232, 238, 244, 250, 252, 258, 268 , 278, 288, 294, 296, 302, 308, 310, 316, 326, 336, 355, 357, 373, 383, 393, 403, 413, 423, 438, 448, 458, 468, 478, 488, 498 , 508, 518, 528, 538, 548, 558, 568, 578, 588, 598, 608, 618, 686, 696, 744, and 746, wherein the variation is optionally limited to one or more framework regions and/or the variation Contains one or more substitutions to a germline encoded amino acid. The antibody or antigen-binding fragment of any one of claims 1 to 12, wherein the VH comprises an amino acid sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO.:399 or consists of, and the VL comprises or consists of an amino acid sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738. The antibody or antigen-binding fragment of any one of claims 1 to 13, wherein the VH comprises an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO.:399 or consists of, and the VL comprises or consists of an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738. The antibody or antigen-binding fragment of any one of claims 1 to 14, wherein the VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO.:399 or consists of, and the VL comprises or consists of an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738. The antibody or antigen-binding fragment of any one of claims 1 to 15, wherein the VH comprises an amino acid sequence that is at least 97% identical to the amino acid sequence set forth in SEQ ID NO.:399 or consists of, and the VL comprises or consists of an amino acid sequence that is at least 97% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738. The antibody or antigen-binding fragment of any one of claims 1 to 16, wherein the VH comprises an amino acid sequence that is at least 99% identical to the amino acid sequence set forth in SEQ ID NO.:399 or consists of, and the VL comprises or consists of an amino acid sequence that is at least 99% identical to the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738. The antibody or antigen-binding fragment of any one of claims 1 to 12, wherein the VH and the VL are at least 85% identical to the amino acid sequences set forth below (eg, 85%, 86%, 87%) %, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%): (i) are SEQ ID NOs.: 524 and 528, respectively; (ii) are SEQ ID NOs.: 584 or 624 or 626 or 628, respectively; and 588; (iii) SEQ ID NOs.: 228 or 740 or 741 or 742 or 743; and 232, respectively; or (iv) are SEQ ID NOs.: 228 or 740 or 741 or 742 or 743; and 238, respectively. The antibody or antigen-binding fragment of any one of claims 1 to 18, wherein the VH comprises or consists of any VH amino acid sequence set forth in Table 2, and wherein the VL comprises any of the VH amino acid sequences set forth in Table 2 VL amino acid sequence or consisting of, wherein optionally, the VH and the VL comprise or consist of the amino acid sequence according to the following: (i) SEQ ID NOs.: 399; and 403 or 738, respectively; (ii) are SEQ ID NOs.: 32 and 36, respectively; (iii) SEQ ID NOs.: 42 and 46, respectively; (iv) are SEQ ID NOs.: 52 and 56, respectively; (v) are SEQ ID NOs.: 62 and 66, respectively; (vi) SEQ ID NOs.: 72 and 66, respectively; (vii) are SEQ ID NOs.: 74 and 78, respectively; (viii) are SEQ ID NOs.: 84 and 88, respectively; (ix) are SEQ ID NOs.: 84 and 88, respectively; (x) are respectively SEQ ID NOs.: 96 and 100; (xi) are respectively SEQ ID NOs.: 106 and 110; (xii) SEQ ID NOs.: 119 and 123, respectively; or (xiii) are SEQ ID NOs.: 129 and 133, respectively; (xiv) are SEQ ID NOs.: 22 or 150; and 26, 154 or 157, respectively; (xv) are SEQ ID NOs.: 42 or 163; and 46 or 168, respectively; (xvi) are any of SEQ ID NOs.: 129, 173, 175 or 178 and 133, respectively; (xvii) are SEQ ID NOs.: any one of 52, 186, 189 or 191 and any one of 56, 194 or 196, respectively; (xviii) are SEQ ID NOs.: 198 and 202, respectively; (xix) are respectively SEQ ID NOs.: 208 and 212; (xx) are respectively SEQ ID NOs.: 218 and 222; (xxi) are SEQ ID NOs.: 228 and 232 or 238, respectively; (xxii) are SEQ ID NOs.: 240, and any one of 244, 250, or 252, respectively; (xxiii) are SEQ ID NOs.: 254 and 258, respectively; (xxiv) are SEQ ID NOs.: 264 and 268, respectively; (xxv) are SEQ ID NOs.: 274 and 278, respectively; or (xxvi) are SEQ ID NOs.: 284, and any one of 288, 294, or 296, respectively; (xxvii) are SEQ ID NOs.: 298, and any one of 302, 308, or 310, respectively; (xxviii) are SEQ ID NOs.: 312 and 316, respectively; (xxix) are SEQ ID NOs.: 322 and 326, respectively; (xxx) are respectively SEQ ID NOs.: 332 and 336; (xxxi) are SEQ ID NOs.: any one of 228, 350, 351 or 353 and any one of 232, 238, 355 or 357, respectively; (xxxii) are any of SEQ ID NOs.: 312, 359, 361, 363, 365, 367 or 368 and 316, respectively; (xxxiii) are SEQ ID NOs.: 369 and 373, respectively; (xxxiv) are SEQ ID NOs.: 379 and 383, respectively; (xxxv) are respectively SEQ ID NOs.: 389 and 393; (xxxvi) are respectively SEQ ID NOs.: 22 and 26; (xxxvii) are respectively SEQ ID NOs.: 409 and 413; (xxxviii) are respectively SEQ ID NOs.: 419 and 423; (xxxix) are SEQ ID NOs.: 434 and 438, respectively; (xxxx) are SEQ ID NOs.: 444 and 448, respectively; (xxxxi) are respectively SEQ ID NOs.: 454 and 458; (xxxxii) are SEQ ID NOs.: 464 and 468, respectively; (xxxxiii) are SEQ ID NOs.: 474 and 478, respectively; (xxxxiv) are SEQ ID NOs.: 484 and 488, respectively; (xxxxv) are SEQ ID NOs.: 494 and 498, respectively; (xxxxvi) are SEQ ID NOs.: 504 and 508, respectively; (xxxxvii) are SEQ ID NOs.: 514 and 518, respectively; (xxxxviii) are SEQ ID NOs.: 524 and 528, respectively; (xxxixix) are SEQ ID NOs.: 534 and 538, respectively; (xxxxx) are SEQ ID NOs.: 544 and 548, respectively; (xxxxxx) are respectively SEQ ID NOs.: 554 and 558; (xxxxxii) are SEQ ID NOs.: 564 and 568, respectively; (xxxxxiii) are SEQ ID NOs.: 574 and 578, respectively; (xxxxxiv) are SEQ ID NOs.: 584 and 588, respectively; (xxxxxv) are SEQ ID NOs.: 594 and 598, respectively; (xxxxxvi) are respectively SEQ ID NOs.: 604 and 608; (xxxxxvii) are respectively SEQ ID NOs.: 614 and 618; (xxxxxviii) are SEQ ID NOs.: 624, 626 or 628; and 588, respectively; (xxxxxix) are SEQ ID NOs.: 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682 or 684; and 686; (xxxxxx) are respectively SEQ ID NOs.: 692 and 696; (xxxxxxi) are any one of SEQ ID NOs.: 740-743 and 238, respectively; (xxxxxxii) are any of SEQ ID NOs.: 399, 748, 749, 750, 752, 754, 756, 758, 759 and 761 and any of 403, 744 and 746, respectively; or (xxxxxxiii) are SEQ ID NOs.: 762 or 764 and 588, respectively. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 399 or is derived therefrom consisting of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 738, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 399 or is derived therefrom consisting of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 403, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NOs: 399, 748, 749, 750, 752, 754, the amino acid sequence set forth in or consisting of any one of 756, 758, 759 and 761, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 403, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NOs: 399, 748, 749, 750, 752, 754, the amino acid sequence set forth in or consisting of any one of 756, 758, 759 and 761, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 738, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NOs: 399, 748, 749, 750, 752, 754, the amino acid sequence set forth in or consisting of any one of 756, 758, 759 and 761, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 744, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises SEQ ID NOs: 399, 748, 749, 750, 752, 754, the amino acid sequence set forth in any one of 756, 758, 759 and 761 or consisting of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 746, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 524 or is derived therefrom consisting of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 528, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises any one of SEQ ID NOs.: 584, 624, 626 and 628 the amino acid sequence set forth in or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 588, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises one of SEQ ID NOs.: 228, 740, 741, 742 and 743 the amino acid sequence set forth in any one of or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 232, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises one of SEQ ID NOs.: 228, 740, 741, 742 and 743 the amino acid sequence set forth in any one of or consists of, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 238, wherein the antibody or antigen-binding fragment is capable of binding to a surface glycoprotein of SARS-CoV-2 expressed on a cell surface of a host cell and/or on a virion. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 32 or is derived therefrom composition, and the VL comprises or consists of the amino acid sequence set forth in SEQ ID NO:36. An antibody or an antigen-binding fragment thereof comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a CDRH1, a CDRH2 and a CDRH3, and The light chain variable domain (VL) comprises a CDRL1, a CDRL2 and a CDRL3, wherein the CDRH1, CDRH2 and CDRH3 respectively comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 33-35 and CDRL1, CDRL2 and CDRL3 respectively comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 37-39. The antibody or antigen-binding fragment of any one of claims 3 to 31, which is capable of neutralizing a SARS-CoV-2 infection in an in vitro infection model and/or an in vivo animal infection model and/or in a human. The antibody or antigen-binding fragment of any one of claims 1 to 32, which: (i) Recognize an epitope in the ACE2 receptor binding motif (RBM, SEQ ID NO.: 5) of SARS-CoV-2; (ii) capable of blocking an interaction between SARS-CoV-2 (eg, SARS-CoV-2 RBM) and human ACE2; (iii) capable of binding to the SARS-CoV-2 S protein; (iv) recognize an epitope conserved in the ACE2 RBM of SARS-CoV-2 and in one of the ACE2 RBMs of SARS-CoV-1; (v) cross-reacts against SARS-CoV-2 and SARS-CoV-1 coronaviruses; (vii) recognizing an epitope in the SARS-CoV-2 surface glycoprotein but not in the ACE2 RBM; (viii) capable of binding to a SARS-CoV-2 S protein trimer in a prefusion conformation; or (ix) any combination of (i)-(viii). The antibody or antigen-binding fragment of any one of claims 1 to 33, which is of an IgG, IgA, IgM, IgE or IgD isotype. The antibody or antigen-binding fragment of any one of claims 1 to 34, which is an IgG isotype selected from the group consisting of IgGl, IgG2, IgG3, and IgG4. The antibody or antigen-binding fragment of any one of claims 1 to 35, which is human, humanized or chimeric. The antibody or antigen-binding fragment of any one of claims 1 to 36, wherein the antibody or the antigen-binding fragment comprises a human antibody, a monoclonal antibody, a purified antibody, a single-chain antibody, a Fab, a Fab' , an F(ab')2, an Fv, an scFv or a scFab. The antibody or antigen-binding fragment of claim 37, wherein the scFv comprises more than one VH domain and more than one VL domain. The antibody or antigen-binding fragment of any one of claims 1 to 38, wherein the antibody or antigen-binding fragment is a multispecific antibody or antigen-binding fragment. The antibody or antigen-binding fragment of claim 39, wherein the antibody or antigen-binding fragment is a bispecific antibody or antigen-binding fragment. The antibody or antigen-binding fragment of claim 39 or 40, comprising: (i) a first VH and a first VL; and (ii) a second VH and a second VL, wherein the first VH and the second VH are different and each independently comprise at least 85% (eg, 85%, 86%, 87%, 88%, 89%) of the amino acid sequence set forth in any of the following %, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical monoamino acid sequences: SEQ ID NOs.: 22, 32, 42, 52, 62, 72, 74, 84, 96, 106, 119, 129, 139, 150, 163, 173, 175, 178, 186, 189, 191, 198, 208, 218, 228, 240, 254, 264, 274, 284, 298, 312, 322, 332, 350, 351, 353, 359, 361, 363, 365, 367, 368, 369, 379, 389, 399, 409, 419, 429, 434, 444, 454, 464, 474, 484, 494, 504, 514, 524, 534, 544, 554, 564, 574, 584, 594, 604, 614, 624, 626, 628, 630, 634, 636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 692, 740, 741, 742, 743, 748, 749, 750, 752, 754, 756, 758, 759, 761, 762, and 764, and wherein the first VL and the second VL are different and each independently comprise at least 85% (eg, 85%, 86%, 87%, 88%, 89%) of the amino acid sequence set forth in any of the following %, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical monoamino acid sequences: SEQ ID NOs.: 26, 36, 46, 56, 66, 78, 88, 94, 100, 110, 123, 133, 143, 154, 157, 168, 194, 196, 202, 212, 222, 232, 238, 244, 250, 252, 258, 268, 278, 288, 294, 296, 302, 308, 310, 316, 326, 336, 355, 357, 373, 383, 393, 403, 413, 423, 438, 448, 458, 468, 478, 488, 498, 508, 518, 528, 538, 548, 558, 568, 578, 588, 598, 608, 618, 686, 696 738, 744 and 746; And wherein the first VH and the first VL together form a first antigen binding site, and wherein the second VH and the second VL together form a second antigen binding site. The antibody or antigen-binding fragment of claim 40 or 41, comprising: (i) a first VH and a first VL; and (ii) a second VH and a second VL, wherein the first VH comprises at least 85% (e.g., 85%, 86%, 87%, 88%, 89%, 90%) of the amino acid sequence set forth in any one of SEQ ID NO.: 139 and 342 %, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical monoamino acid sequences, and the first VL comprises the The amino acid sequence set forth in any of ID NO.: 143 and 346 has at least 85% (ie, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%) , 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical amino acid sequence, and wherein the second VH comprises and SEQ ID NO.: 399, The amino acid sequence set forth in any one of 748, 749, 750, 752, 754, 756, 758, 759, and 761 has at least 85% (e.g., 85%, 86%, 87%, 88%, 89% , 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical monoamino acid sequences and the second VL comprises have at least 85% (i.e., 85%, 86%, 87%, 88%, 89%, 90%, 91%) of the amino acid sequence set forth in any of SEQ ID NO. %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical monoamino acid sequences. The antibody or antigen-binding fragment of claim 39 or 40, comprising a first antigen-binding portion with a first specificity and a second antigen-binding portion with a second specificity, wherein the first antigen-binding portion comprising a VH comprising or consisting of the amino acid sequence set forth in SEQ ID NO:399 and a VL comprising the amine set forth in SEQ ID NO.:738 or SEQ ID NO.:403 amino acid sequence or consist of it. The antibody or antigen-binding fragment of claim 43, wherein the second antigen-binding portion comprises a VH and a VL, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 139, and the VL comprises The amino acid sequence set forth in or consisting of SEQ ID NO.:143. The antibody or antigen-binding fragment of claim 43, wherein the second antigen-binding portion comprises a VH and a VL, the VH comprises or consists of the amino acid sequence set forth in SEQ ID NO: 342, and the VL comprises The amino acid sequence set forth in or consisting of SEQ ID NO.:346. The antibody or antigen-binding fragment of any one of claims 1 to 45, wherein the antibody or antigen-binding fragment further comprises an Fc polypeptide or a fragment thereof. The antibody or antigen-binding fragment of claim 46, wherein the Fc polypeptide or fragment thereof comprises: (i) a mutation that enhances binding to an FcRn compared to a reference Fc polypeptide not comprising the mutation; and/or (ii) a mutation that enhances binding to an FcyR compared to a reference Fc polypeptide that does not contain the mutation. The antibody or antigen-binding fragment of claim 47, wherein the mutation that enhances binding to an FcRn comprises: M428L; N434S; N434H; N434A; N434S; M252Y; S254T; T256E; T250Q; P257I; Q311I; D376V; or any combination thereof. The antibody or antigen-binding fragment of claim 47 or 48, wherein the mutation that enhances binding to FcRn comprises: (i) M428L/N434S; (ii) M252Y/S254T/T256E; (iii) T250Q/M428L; (iv) P257I/Q311I; (v) P257I/N434H; (vi) D376V/N434H; (vii) T307A/E380A/N434A; or (viii) any combination of (i)-(vii). The antibody or antigen-binding fragment of any one of claims 47 to 49, wherein the mutation that enhances binding to FcRn comprises M428L/N434S. The antibody or antigen-binding fragment of any one of claims 47 to 50, wherein the mutation that enhances binding to an FcyR comprises S239D; I332E; A330L; G236A; or any combination thereof. The antibody or antigen-binding fragment of any one of claims 47 to 51, wherein the mutation that enhances binding to an FcγR comprises: (i) S239D/I332E; (ii) S239D/A330L/I332E; (iii) G236A/S239D/I332E; or (iv) G236A/A330L/I332E. The antibody or antigen-binding fragment of any one of claims 47 to 52, wherein the Fc polypeptide comprises an L234A mutation and a L235A mutation. The antibody or antigen-binding fragment of any one of claims 1 to 53, comprising a mutation that alters glycosylation, wherein the mutation that alters glycosylation comprises N297A, N297Q or N297G, and/or the antibody or antigen binds Fragments are deglycosylated and/or defucosylated. The antibody or antigen-binding fragment of any one of claims 1 to 54, which is capable of binding to a SARS-CoV-2 surface glycoprotein with an EC50 of one of: below 500 ng/ml, below 250 ng/ml, Below 100 ng/ml, Below 90 ng/ml, Below 80 ng/ml, Below 70 ng/ml, Below 60 ng/ml, Below 50 ng/ml, Below 40 ng/ml, Low below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 16 ng/ml, below 15 ng/ml, below 14 ng/ml, below 13 ng/ml, below 12 ng/ml, below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 ng/ml, below 4 ng/ml or less than 2 mg/ml, as measured by ELISA (optionally, indirect ELISA and/or sandwich ELISA) and/or by flow cytometry, wherein the SARS CoV-2 surface sugar The protein is expressed on the cell surface of one of the host cells. The antibody or antigen-binding fragment of any one of claims 1 to 55, which is capable of binding to a SARS-CoV-2 surface glycoprotein RBD with one of the following EC50s: below 500 ng/ml, below 250 ng/ml , below 100 ng/ml, below 90 ng/ml, below 80 ng/ml, below 70 ng/ml, below 60 ng/ml, below 50 ng/ml, below 40 ng/ml, Below 30 ng/ml, Below 25 ng/ml, Below 20 ng/ml, Below 16 ng/ml, Below 15 ng/ml, Below 14 ng/ml, Below 13 ng/ml, Low below 12 ng/ml, below 10 ng/ml, below 9 ng/ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 ng/ml, below 4 ng/ml or less than 2 mg/ml, as measured by ELISA (optionally, indirect ELISA and/or sandwich ELISA) and/or by flow cytometry, wherein the SARS CoV-2 surface Glycoproteins are expressed on the cell surface of one of the host cells. The antibody or antigen-binding fragment of any one of claims 1 to 56, which is capable of binding to a SARS-CoV-2 RBD with one of the following KDs: below 5 × 10 ^-8 M, below 4 × 10 ^-8 M, below 3 × 10 ^-8 M, below 2 × 10 ^-8 M, below 1 × 10 ^-8 M, below 5 × 10 ^-9 M, below 1 × 10 ^-9 M, below 5 × 10 ^-10 M, below 1 × 10 ^-10 M, below 5 × 10 ^-11 M, below 1 × 10 ^-11 M, below 5 × 10 ^-12 M, or below 1 × 10 ^-12 M , as determined using biolayer interferometry (BLI), optionally using an Octet instrument with antibody or antigen-binding fragment loaded on a protein A needle optionally at 2.7 µg/ml, and SARS- CoV-2 RBDs were loaded at 6 µg/ml, 1.5 µg/ml, or 0.4 µg/ml for 5 minutes, and further dissociation was optionally measured for 7 minutes. The antibody or antigen-binding fragment of any one of claims 1 to 57, which is capable of binding to a SARS-CoV-2 RBD with one of the following KDs: below 6 × 10 ^-8 M, below 5 × 10 ^-8 M, below 4 × 10 ^-8 M, below 3 × 10 ^-8 M, below 2 × 10 ^-8 M, below 1 × 10 ^-8 M, below 5 × 10 ^-9 M, below 4 × 10 ^-9 M, below 3 × 10 ^-9 M, below 2 × 10 ^-9 M, below 1 × 10 ^-9 M, or below 8 × 10 ^-10 M, if using surface plasmon resonance ( SPR), optionally determined using a single cycle kinetic method using a Biacore T200 instrument. The antibody or antigen-binding fragment of any one of claims 1 to 58, which is capable of binding to a SARS-CoV-2 RBD and inhibiting (i) the RBD and (ii) a human ACE2 and/or a human SIGLEC- an interaction between 1. The antibody or antigen-binding fragment of any one of claims 1 to 59, which is capable of neutralizing: (i) Infection by a SARS-CoV-2 pseudovirus, optionally: (i)(a) has a neutralizing IC50 of less than 100 ng/ml, less than 90 ng/ml, less than 80 ng/ml, less than 70 ng/ml, less than 60 ng/ml, less than 50 ng/ml ng/ml, below 40 ng/ml, below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 15 ng/ml, below 10 ng/ml, below 9 ng /ml, below 8 ng/ml, below 7 ng/ml, below 6 ng/ml, below 5 ng/ml, below 4 ng/ml, below 3 ng/ml, below 2 ng/ml ml or less than 1 ng/ml, preferably less than 10 ng/ml, less than 9 ng/ml, less than 8 ng/ml, less than 7 ng/ml, less than 6 ng/ml, less than 5 ng /ml, less than 4 ng/ml, less than 3 ng/ml, less than 2 ng/ml, or less than 1 ng/ml, and/or (i)(b) has a neutralizing IC80 of less than 100 ng/ml, less than 90 ng/ml, less than 80 ng/ml, less than 70 ng/ml, less than 60 ng/ml, less than 50 ng/ml ng/ml, below 40 ng/ml, below 30 ng/ml or below 25 ng/ml, preferably below 50 ng/ml, below 40 ng/ml, below 30 ng/ml or below 25 ng/ml, and/or (i)(c) has a neutralizing EC90 of less than 300 ng/ml, less than 200 ng/ml, less than 100 ng/ml, less than 90 ng/ml, less than 80 ng/ml, less than 70 ng/ml ng/ml, below 60 ng/ml 50 ng/ml, below 40 ng/ml, below 30 ng/ml, below 25 ng/ml, below 20 ng/ml, below 15 ng/ml or less than 10 ng/ml, wherein further optionally, the SARS-CoV-2 pseudovirus comprises a VSV pseudovirus and/or an MLV pseudovirus, and/or (i)(d) the SARS-CoV-2 pseudovirus comprises a VSV pseudovirus and/or an MLV pseudovirus; and/or (ii) infection by live SARS-CoV-2, optionally (ii)(a) has an EC50 of less than 60 ng/ml, less than 50 ng/ml, less than 40 ng/ml, less than 30 ng/ml, less than 25 ng/ml, less than 20 ng/ml ml, less than 15 ng/ml, less than 12 ng/ml, less than 11 ng/ml, less than 10 ng/ml, less than 9 ng/ml, less than 8 ng/ml, less than 7 ng/ml , below 6 ng/ml, below 5/ng ml or below 4 ng/ml, preferably below 15 ng/ml, below 12 ng/ml, below 11 ng/ml, below 10 ng/ml ml, less than 9 ng/ml, less than 8 ng/ml, less than 7 ng/ml, less than 6 ng/ml, less than 5/ng ml, or less than 4 ng/ml, and/or (ii)(b) has an EC90 of less than 50 ng/ml, less than 40 ng/ml, less than 35 ng/ml, less than 30 ng/ml, less than 25 ng/ml, less than 20 ng/ml ml, less than 15 ng/ml, less than 12 ng/ml, less than 11 ng/ml, less than 10 ng/ml, less than 9 ng/ml, less than 8 ng/ml, less than 7 ng/ml , less than 6 ng/ml, less than 5/ng ml or less than 4 ng/ml, preferably less than 30 ng/ml, less than 25 ng/ml, less than 20 ng/ml, less than 15 ng/ml ml or less than 12 ng/ml, and/or (ii)(c) has an infection multiplier of 0.1 during a 6-hour period; and/or (iii) Infection by live SARS-CoV-2 in a host cell (eg, a HEK293T cell) expressing, optionally engineered to overexpress DC-SIGN, L-SIGN, SIGLEC or ACE2; and/or (iv) infection by live SARS-CoV-2 in a host cell (eg, a HEK293T cell) that expresses, optionally engineered to overexpress SIGLEC-1 or ACE2, wherein neutralization Infection consists of completely neutralizing the infection. The antibody or antigen-binding fragment of any one of claims 1 to 60, which is capable of neutralizing infection caused by a SARS-CoV-2 variant, and comprising a SARS-CoV-2 surface carbohydrate comprising one of SEQ ID NO.: 3 Compared to protein, the SARS-CoV-2 variant contains any of the following mutations in the surface glycoprotein: N501Y; S477N; N439K; L452R; E484K; K417N; T478K; S494P; A520S; N501T; A522S; Y453F ; P384L. The antibody or antigen-binding fragment of claim 61, which is capable of neutralizing infection caused by the SARS-CoV-2 variant with an efficacy that is less than 3-fold lower than neutralization by the antibody or antigen-binding fragment Efficacy of infection by SARS-CoV-2, one of the surface glycoprotein amino acid sequences set forth in SEQ ID NO.:3. The antibody or antigen-binding fragment of any one of claims 1 to 62, which is capable of activating an FcyRIIa, an FcyRIIIa, or both, wherein optionally: (i) the FcyRIIa comprises an H131 counterpart gene; and/or (ii) the FcγRIIIa comprises a V158 counterpart gene; and/or (iii) Activation is assayed using a target cell expressing SARS-CoV-2 S, such as a CHO cell, and a reporter cell expressing an NFAT-driven reporter, such as luciferase. The antibody or antigen-binding fragment of any one of claims 1 to 63, comprising: (a) the CH1-CH3 amino acid sequence set forth in SEQ ID NO.:6 and the CL amino acid sequence set forth in SEQ ID NO.:8; (b) the CH1-CH3 amino acid sequence set forth in SEQ ID NO.:6 and the CL amino acid sequence set forth in SEQ ID NO.:9; (c) the CH1-CH3 amino acid sequence set forth in SEQ ID NO.:7 and the CL amino acid sequence set forth in SEQ ID NO.:8; or (d) the CH1-CH3 amino acid sequence set forth in SEQ ID NO.:7 and the CL amino acid sequence set forth in SEQ ID NO.:9. An isolated antibody comprising: (i) the heavy chain amino acid sequence set forth in SEQ ID NO.:767; and (ii) the light chain amino acid sequence set forth in SEQ ID NO.:768. The antibody or antigen-binding fragment of any one of claims 1 to 65, which has an in vivo half-life in a non-human primate of between 20 and 30 days, or between 22 and 28 days, or Between 23 and 27 days, or between 24 and 26 days, or about 25 days. The antibody or antigen-binding fragment of any one of claims 1 to 66, wherein the antibody or antigen-binding fragment is capable of neutralizing a SARS-CoV-2 infection and/or with an IC50 of about 20 to about 30 ng/ml Neutralize infection of one of the target cells. The antibody or antigen-binding fragment of any one of claims 1 to 66, wherein the antibody or antigen-binding fragment is capable of neutralizing a SARS-CoV-2 infection and/or with an IC50 of about 10 to about 20 ng/ml Neutralize infection of one of the target cells. The antibody or antigen-binding fragment of any one of claims 1 to 66, wherein the antibody or antigen-binding fragment is capable of neutralizing a SARS-CoV-2 infection and/or with an IC50 of about 5 to about 10 ng/ml Neutralize infection of one of the target cells. The antibody or antigen-binding fragment of any one of claims 1 to 66, wherein the antibody or antigen-binding fragment is capable of neutralizing a SARS-CoV-2 infection and/or an IC50 of about 1 to about 5 ng/ml Neutralize infection of one of the target cells. The antibody or antigen-binding fragment of any one of claims 1 to 70, wherein the antibody or antigen-binding fragment is capable of neutralizing infection caused by SARS-CoV-2 and does not compete with a human ACE2 for binding to the SARS-CoV-2 CoV-2S protein, Optionally, the neutralizing comprises neutralizing infection in an in vitro infection model. An antibody or an antigen-binding fragment thereof that competes with the antibody or antigen-binding fragment of any one of claims 1 to 71 for binding to a SARS-CoV-2 surface glycoprotein. An isolated polynucleotide encoding the antibody or antigen-binding fragment of any one of claims 1 to 72, or encoding a VH, a heavy chain, a VL and/or a VH of the antibody or the antigen-binding fragment light chain. The polynucleotide of claim 73, wherein the polynucleotide comprises deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), wherein the RNA optionally comprises messenger RNA (mRNA). The polynucleotide of claim 73 or 74, which is codon-optimized for expression in a host cell. The polynucleotide of any one of claims 73 to 75, comprising at least 50%, at least 55%, at least 60%, at least 65% with the polynucleotide sequence according to any one or more of the following %, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identical, or including according to any one or more of the following The polynucleotide sequence or a polynucleotide consisting of: SEQ ID NOs.: 30, 31, 40, 41, 50, 51, 60, 61, 70, 71, 73, 82, 83, 92 , 93, 95, 104, 105, 114, 115, 116, 117, 118, 127, 128, 137, 138, 206, 207, 216, 217, 226, 227, 236, 237, 239, 248, 249, 251 , 253, 262, 263, 272, 273, 282, 283, 292, 293, 295, 297, 306, 307, 309, 311, 320, 321, 330, 331, 340, 341, 377, 378, 387, 388 , 397, 398, 407, 408, 417, 418, 427, 428, 433, 442, 443, 452, 453, 462, 463, 472, 473, 482, 483, 492, 493, 502, 503, 512, 513 , 552, 523, 532, 533, 542, 543, 552, 553, 562, 563, 572, 573, 582, 583, 592, 593, 602, 603, 612, 613, 622, 623, 690, 691, 700 -737 and 739. The polynucleotide of any one of claims 73 to 76, comprising: (i) at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85% of the nucleotide sequence set forth in SEQ ID NO.:407 , at least 90%, at least 95%, at least 97%, or at least 99% identical, or a polynucleotide comprising or consisting of the nucleotide sequence set forth in SEQ ID NO.:407; and (ii) at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80% of the nucleotide sequence set forth in SEQ ID NOs.: 408, 737 or 739 , at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identical, or comprising or consisting of a nucleotide sequence set forth in SEQ ID NOs.: 408, 737 or 739 a polynucleotide. A recombinant vector comprising the polynucleotide of any one of claims 73 to 77. A host cell comprising the polynucleotide of any one of claim 77 and/or the vector of claim 78, wherein the polynucleotide is heterologous to the host cell. A human B cell comprising the polynucleotide of any one of claims 73 to 77, wherein the polynucleotide is heterologous to the human B cell and/or wherein the human B cell is immortalized . A composition comprising: (i) the antibody or antigen-binding fragment of any one of claims 1 to 72; (ii) the polynucleotide of any one of claims 73 to 77; (iii) the recombinant vector of claim 78; (iv) the host cell of claim 79; and/or (v) the human B cell of claim 80, and a pharmaceutically acceptable excipient, carrier or diluent. The composition of claim 81, comprising two or more antibodies or antigen-binding fragments of any one of claims 1 to 72. The composition of claim 82, comprising: (i) a first antibody or antigen-binding fragment comprising a VH and a VL, the VH comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 32, and the VL comprising, as SEQ ID NO: 32 : the amino acid sequence set forth in or consist of 36; and (ii) a second antibody or antigen-binding fragment comprising a VH and a VL, the VH comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 139, and the VL comprising as in SEQ ID NO : The amino acid sequence set forth in 143 or consists of it. The composition of claim 82, comprising: (i) a first antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a CDRH1, a CDRH2 and a CDRH3, and the light chain variable domain (VL) comprises a CDRL1, a CDRL2 and a CDRL3, wherein the CDRH1, CDRH2 and CDRH3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 33-35 or consist of the consisting of amino acid sequences, and the CDRL1, CDRL2 and CDRL3 respectively comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 37-39; and (ii) a second antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a CDRH1, a CDRH2 and a CDRH3, and the light chain variable domain (VL) comprises a CDRL1, a CDRL2 and a CDRL3, wherein the CDRH1, CDRH2 and CDRH3 respectively comprise the amino acid sequences set forth in SEQ ID NOs: 140-142 or are composed of these amino acid sequences, and the CDRL1, CDRL2 and CDRL3 respectively comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 144-146. The composition of claim 82, comprising: (i) a first antibody or antigen-binding fragment comprising a VH and a VL, the VH comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 139 or 342, and the VL comprising as SEQ ID NO: 139 or 342 The amino acid sequence set forth in ID NO: 143 or 346 or consists of it; and (ii) a second antibody or antigen-binding fragment comprising a VH and a VL, the VH comprising as set forth in SEQ ID NO: 399, 748, 749, 750, 752, 754, 756, 758, 759 or 761 and the VL comprises or consists of the amino acid sequence as set forth in SEQ ID NO: 403, 744 or 746. The composition of claim 82, comprising: (i) a first antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a CDRH1, a CDRH2 and a CDRH3, and the light chain variable domain (VL) comprises a CDRL1, a CDRL2 and a CDRL3, wherein the CDRH1, CDRH2 and CDRH3 comprise set forth in SEQ ID NOs: 140-142, respectively, or SEQ ID NOs: 343-345, respectively The amino acid sequence of or consists of these amino acid sequences, and the CDRL1, CDRL2 and CDRL3 respectively comprise or consist of the amino acid sequences set forth in SEQ ID NOs: 144-146; and (ii) a second antibody or antigen-binding fragment comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), the heavy chain variable domain (VH) comprising a CDRH1, a CDRH2 and a CDRH3, and the light chain variable domain (VL) comprises a CDRL1, a CDRL2 and a CDRL3, wherein the CDRH1, CDRH2 and CDRH3 comprise SEQ ID NOs: 400, 401 and 751, 753, 755, 757, 760, respectively The amino acid sequences set forth in any one of or consist of such amino acid sequences, and the CDRL1, CDRL2 and CDRL3 comprise the amino acid sequences set forth in any of SEQ ID NOs: 404, 405 and 406, 745 and 747, respectively The stated amino acid sequences are or consist of such amino acid sequences. A composition comprising: (i) a first antibody or antigen-binding fragment comprising (i) (a) a VH comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 32, and (i) (b) a VL comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 36; and (ii) a second antibody or antigen-binding fragment comprising (ii) (a) a VH comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 139, and (ii) (b) a VL comprising or consisting of the amino acid sequence as set forth in SEQ ID NO: 143. A composition comprising: (i) a primary antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein, comprising (i) (a) a VH comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences as set forth in SEQ ID NOs.: 400, 402 and 766, respectively, and (i) (b) a VL comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences as set forth in SEQ ID NOs.: 404, 405 and 406, respectively; and (ii) a second antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein, comprising (ii) (a) a VH comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences as set forth in SEQ ID NOs.: 140, 141 or 343 and 142, respectively, and (ii) (b) a VL comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences as set forth in SEQ ID NOs.: 144, 145 and 146, respectively. A composition comprising: (i) a primary antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein, comprising (i) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO.:399, and (i) (b) a VL comprising the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738; and (ii) a second antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein, comprising (ii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO.: 139 or 342, and (ii) (b) a VL comprising the amino acid sequence set forth in SEQ ID NO.:143. The composition of any one of claims 82 to 89, wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment each comprise an IgG1 Fc polypeptide comprising an M428L mutation and an N434S mutation. The composition of any one of claims 82 to 90, wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment each comprise an IgG1 Fc polypeptide comprising a G236A mutation, an A330L mutation, and a I332E mutation. A composition comprising the polynucleotide of any one of claims 73 to 77 encapsulated in a carrier molecule, wherein the carrier molecule optionally comprises a lipid, a lipid-derived delivery vehicle , such as a liposome, a solid lipid nanoparticle, an oily suspension, a micron-sized lipid emulsion, a lipid microbubble, a retrolipid micelle, a cochlear liposome, a lipid microtubule, a lipid micropillar, Lipid Nanoparticles (LNPs) or a nanoscale platform. A composition comprising: (i) a primary antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with ACE2, DC-SIGN, L-SIGN and an interaction between one of the first cell surface receptors of SIGLEC-1; and (ii) a second antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with the group consisting of ACE2, DC-SIGN, L-SIGN and An interaction between one of the second cell surface receptors of SIGLEC-1, wherein the first cell surface receptor is different from the second cell surface receptor. A method of treating a coronavirus infection, such as a SARS-CoV-2 infection in an individual, the method comprising administering to the individual an effective amount of: (i) the antibody or antigen-binding fragment of any one of claims 1 to 72; (ii) the polynucleotide of any one of claims 73 to 77; (iii) the recombinant vector of claim 78; (iv) the host cell of claim 79; (v) human B cells as claimed in claim 80; and/or (vi) The composition of any one of claims 81 to 93. A method of treating a coronavirus infection in an individual, such as a SARS-CoV-2 infection, the method comprising administering to the individual: (i) a primary antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein, comprising (i) (a) a VH comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences as set forth in SEQ ID NOs.: 400, 402 and 766, respectively, and (i) (b) a VL comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences as set forth in SEQ ID NOs.: 404, 405 and 406, respectively; and (ii) a second antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein, comprising (ii) (a) a VH comprising the CDRH1, CDRH2 and CDRH3 amino acid sequences as set forth in SEQ ID NOs.: 140, 141 or 343 and 142, respectively, and (ii) (b) a VL comprising the CDRL1, CDRL2 and CDRL3 amino acid sequences as set forth in SEQ ID NOs.: 144, 145 and 146, respectively. A method of treating a coronavirus infection in an individual, such as a SARS-CoV-2 infection, the method comprising administering to the individual: (i) a primary antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein, comprising (i) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO.:399, and (i) (b) a VL comprising the amino acid sequence set forth in SEQ ID NO.:403 or SEQ ID NO.:738; and (ii) a second antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein, comprising (ii) (a) a VH comprising the amino acid sequence set forth in SEQ ID NO.: 139 or 342, and (ii) (b) a VL comprising the amino acid sequence set forth in SEQ ID NO.:143. A method of preventing or treating or neutralizing a coronavirus infection in an individual, the method comprising: administering a second antibody or antigen-binding fragment to an individual who has received a first antibody or antigen-binding fragment, the first Antibodies or antigen-binding fragments include: (i) (a) VH and VL amino acid sequences according to SEQ ID NOs.: 32 and 36, respectively; or (i) (b) CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NOs.: 33-35 and 37-39, respectively; The second antibody or antigen-binding fragment comprises: (ii) (a) according to a VH amino acid sequence of SEQ ID NO.: 139 and according to a VL amino acid sequence of SEQ ID NO: 143; or (ii)(b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to SEQ ID NOs: 140-142, respectively, and CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NOs: 144-146, respectively. A method of preventing or treating or neutralizing a coronavirus infection in an individual, the method comprising: administering a second antibody or antigen-binding fragment to an individual who has received a first antibody or antigen-binding fragment, the first antibody or an antigen-binding fragment comprising: (i) (a) according to a VH amino acid sequence of SEQ ID NO.: 139 and according to a VL amino acid sequence of SEQ ID NO: 143; or (i) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to SEQ ID NOs: 140-142, respectively; and CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NOs: 144-146, respectively; The second antibody or antigen-binding fragment comprises: (ii) (a) VH and VL amino acid sequences according to SEQ ID NOs.: 32 and 36, respectively; or (ii) (b) CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 amino acid sequences according to SEQ ID NOs.: 33-35 and 37-39, respectively. A method of preventing or treating or neutralizing a coronavirus infection in an individual, the method comprising: administering a second antibody or antigen-binding fragment to an individual who has received a first antibody or antigen-binding fragment, the first antibody or an antigen-binding fragment comprising: (i) (a) a VH amino acid sequence according to one of SEQ ID NO.: 139 or 342 and a VL amino acid sequence according to one of SEQ ID NO: 143 or 346; or (i) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to SEQ ID NOs: 140-142 or SEQ ID NOs: 343-345, respectively; and CDRL1, CDRL2 and CDRL2 according to SEQ ID NOs: 144-146, respectively CDRL3 amino acid sequence; The second antibody or antigen-binding fragment comprises: (ii) (a) a VH amino acid sequence according to one of SEQ ID NO: 399, 748, 749, 750, 752, 754, 756, 758, 759 or 761, and a VH amino acid sequence according to SEQ ID NO: 403, 744 or 746 a VL amino acid sequence; or (ii) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to any one of SEQ ID NOs: 400, 401 and 751, 753, 755, 757, 760, respectively, and according to SEQ ID NOs: 404, CDRL1, CDRL2 and CDRL3 amino acid sequences of any of 405 and 406, 745 and 747. A method of preventing or treating or neutralizing a coronavirus infection in an individual, the method comprising: administering a second antibody or antigen-binding fragment to an individual who has received a first antibody or antigen-binding fragment, the first antibody or an antigen-binding fragment comprising: (i) (a) a VH amino acid sequence according to one of SEQ ID NO: 399, 748, 749, 750, 752, 754, 756, 758, 759 or 761, and a VH amino acid sequence according to SEQ ID NO: 403, 744 or 746 a VL amino acid sequence; or (i) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to any one of SEQ ID NOs: 400, 401 and 751, 753, 755, 757, 760, respectively, and according to SEQ ID NOs: 404, CDRL1, CDRL2 and CDRL3 amino acid sequences of any of 405 and 406, 745 and 747; The second antibody or antigen-binding fragment comprises: (ii) (a) a VH amino acid sequence according to one of SEQ ID NO.: 139 or 342 and a VL amino acid sequence according to one of SEQ ID NO: 143 or 346; or (ii) (b) CDRH1, CDRH2 and CDRH3 amino acid sequences according to SEQ ID NOs: 140-142 or SEQ ID NOs: 343-345, respectively; and CDRL1, CDRL2 and CDRL2 according to SEQ ID NOs: 144-146, respectively CDRL3 amino acid sequence. The method of any one of claims 95 to 100, wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment each comprise an IgGl Fc polypeptide comprising an M428L mutation and an N434S mutation. The method of any one of claims 95 to 101, wherein the first antibody or antigen-binding fragment and the second antibody or antigen-binding fragment each comprise an IgG1 Fc polypeptide comprising a G236A mutation, an A330L mutation, and an I332E mutation. A method of treating a SARS-CoV-2 infection in an individual, the method comprising administering to the individual: (i) a primary antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with ACE2, DC-SIGN, L-SIGN and an interaction between one of the first cell surface receptors of SIGLEC-1; and (ii) a second antibody or antigen-binding fragment capable of binding to a SARS-CoV-2 surface glycoprotein and inhibiting the SARS-CoV-2 surface glycoprotein from interacting with the group consisting of ACE2, DC-SIGN, L-SIGN and An interaction between one of the second cell surface receptors of SIGLEC-1, wherein the first cell surface receptor is different from the second cell surface receptor. The antibody or antigen-binding fragment of any one of claims 1 to 72, the polynucleotide of any one of claims 73 to 77, the recombinant vector of claim 78, the host cell of claim 79, the The human B cell of claim 80 and/or the composition of any one of claims 81 to 93, for use in a method of treating a SARS-CoV-2 infection in an individual. The antibody or antigen-binding fragment of any one of claims 1 to 72, the polynucleotide of any one of claims 73 to 77, the recombinant vector of claim 78, the host cell of claim 79, the The human B cell of claim 80 and/or the composition of any one of claims 81 to 93, for use in the preparation of a medicament for the treatment of a SARS-CoV-2 infection in a subject. A method for in vitro diagnosis of a SARS-CoV-2 infection, the method comprising: (i) contacting a sample from an individual with the antibody or antigen-binding fragment of any one of claims 1 to 72; and (ii) detecting a complex comprising an antigen and the antibody or comprising an antigen and the antigen-binding fragment. The method of claim 106, wherein the sample comprises blood isolated from the individual.

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