CN115006395B - Application of XL888 in preparation of medicine for resisting adenovirus infection - Google Patents

Abstract

The invention belongs to the technical field of biomedicine, and discloses application of XL888 in preparation of a medicament for resisting adenovirus infection, wherein the medicament for relieving and/or preventing and/or treating adenovirus infection acts by inhibiting the activity of adenovirus replication. The adenovirus is various adenovirus types including but not limited to AdV3 subtype, adV5 subtype. A medicament for the alleviation and/or prevention and/or treatment of adenoviral infection comprises XL888 and a pharmaceutically acceptable carrier. The invention provides application of a small molecular compound XL888 in preparation of a medicament for treating adenovirus infection, and provides a safe and effective small molecular compound for clinical treatment of adenovirus. XL888 can effectively inhibit replication of adenovirus in a nontoxic range, can be further developed into a medicament for treating diseases caused by adenovirus infection, and has wide application prospect.

Description

A kind of application of XL888 in the preparation of medicine for anti-adenovirus infection

technical field

The invention belongs to the technical field of biomedicine, and in particular relates to an application of XL888 in the preparation of medicines for resisting adenovirus infection.

Background technique

At present, human adenovirus (Human adenovirus, HAdV) belongs to the mammalian adenovirus genus of the family Adenoviridae. Adenovirus is a DNA virus with no envelope and icosahedral nucleocapsid. The core of the virus genome is a linear double-stranded DNA molecule, about 36kb, and its genome is highly condensed and packaged, and it is composed of hundreds of similar The histone protein VII and the protamine-like protein Mu (also known as protein X) organize chromatin. The capsid of adenovirus has 240 hexon proteins (hexons), and the 12 tips of the icosahedral capsid are complexes composed of pentameric proteins (penton) and trimeric proteins (fiber). Twelve fiber proteins protrude from the surface of the capsid based on the penton protein, and the top of the fiber forms the head section (knob). The knob regions of penton protein and fiber protein can bind to virus receptors on the cell surface, and play a very important role in the process of virus infection of cells. The smaller capsid proteins IIIa, VI, VIII and IX are embedded in the capsid, with capsid protein VI located on the inner surface of the capsid, and capsid protein V connecting the capsid to the core containing the viral genome. There is also a small amount of capsid protein IVa2 involved in genome packaging and adenovirus protease (AVP) formation in the capsid.

Adenovirus infection can occur in any season, but often winter and early spring are the peak seasons for viral infections. Based on serum neutralization, hemagglutination epitopes, genome sequence and function, human adenoviruses are divided into seven species, A, B, C, D, E, F and G, with a total of 57 serotypes. The types of adenoviruses prevalent in my country mainly include type 1, type 3, type 4, type 5, type 7, type 11, type 14, type 40, type 41, and type 55, among which adenovirus type 3 and type 5 are prevalent . Studies have found that except for hexon, fiber, and penton genes, the genomes of various types of adenovirus are highly conserved, and intraspecific recombination rarely occurs. Therefore, it is beneficial to overcome the limitation of drugs on the type-specificity of adenoviruses. Generally, antiviral drugs targeting adenoviruses into later stages have broad-spectrum anti-adenovirus activity within the adenovirus species.

Adenovirus infection has a variety of clinical symptoms and disease manifestations, which largely depend on the type of adenovirus, the immune status of the host, and the site of infection. Common sites of adenovirus infection include the respiratory tract, corneal epithelium, and intestinal tract. Ninety percent of viral conjunctivitis cases are caused by adenovirus infection, usually associated with type B, D, or E adenovirus infection, and often occurs in recruits as pharyngeal conjunctivitis or epidemic keratoconjunctivitis (EKC). B, D or E type adenoviruses also often cause acute respiratory disease and viral pneumonia. Two of the more serious consequences of respiratory adenovirus infection are pneumonia, which can be fatal in children. and acute respiratory distress syndrome, which is more common among conscripts. Type A, F and G adenoviruses have been associated with gastrointestinal infections. Adenovirus infection is the leading cause of gastroenteritis in children, second only to norovirus and rotavirus. Overall, adenoviruses are susceptible to all populations, with more severe disease and even death often occurring in infected neonates, children, and immunocompromised populations (hematopoietic stem cell and organ transplant patients).

There are currently no antiviral drugs approved for the treatment of adenovirus infection. Certain DNA/RNA synthesis-inhibiting antiviral drugs (such as cidofovir, ganciclovir, and ribavirin) approved for the treatment of other viral infections have been approved for clinical treatment of severe Adenovirus infection. However, most of these drugs have limited efficacy and serious adverse reactions. Therefore, it is necessary to develop other safer and more effective anti-adenoviral drugs.

XL888 is a potential new therapeutic agent for the treatment of melanoma, solid tumors and gastrointestinal cancers. It is a novel and potent HSP90 inhibitor that can inhibit the proliferation of various human tumor cell lines. XL888 induces tumor regression by inducing the degradation of relevant oncogenic client proteins in tumor cells, resulting in the blockage of many key oncogenic pathways. However, there is no relevant report on the treatment of adenovirus infection with XL888.

Through the above analysis, the problems and defects in the prior art are:

(1) At present, there is no relevant report on the treatment of adenovirus infection with XL888.

(2) The medicines for the treatment of adenovirus infection in the prior art have low efficacy and poor effect.

Contents of the invention

Aiming at the problems existing in the prior art, the present invention provides a use of XL888 in the preparation of medicaments for resisting adenovirus infection.

The present invention is achieved in the following way, an application of XL888 in the preparation of a medicament for alleviating and/or preventing and/or treating adenovirus infection.

Further, the XL888 structural formula is as follows:

Further, the adenovirus includes AdV3 subtype of type B adenovirus and AdV5 subtype of type C adenovirus.

Further, the adenovirus is one or more of human adenovirus types 1, 3, 4, 5, 7, 11, 14, 40, 41 and 55.

Further, the drug for alleviating and/or preventing and/or treating adenovirus infection works by inhibiting the activity of adenovirus replication.

Further, the drug for alleviating and/or preventing and/or treating adenovirus infection includes XL888 and a pharmaceutically acceptable carrier.

Further, the dosage form of the medicament for alleviating and/or preventing and/or treating adenovirus infection is any clinically acceptable oral dosage form, injection dosage form or external dosage dosage form.

Further, the medicines for alleviating and/or preventing and/or treating adenovirus infection are tablets, capsules, granules, oral liquids, and injections.

Another object of the present invention is to provide a use of XL888 in the preparation of adenovirus inhibitors.

Combining the above-mentioned technical solutions and technical problems to be solved, please analyze the advantages and positive effects of the technical solutions to be protected by the present invention from the following aspects:

The present invention aims at the current situation of antiviral drugs without adenovirus infection in the prior art, combined with the experimental data of low cytotoxicity of XL888 in Vero cells and high antiviral activity against two kinds of adenoviruses in the research and development process, and provides a new anti-adenovirus Virus drug-XL888, provides a new technology of antiviral drugs for adenovirus infection, and provides a new therapy and more treatment options for the treatment of diseases caused by adenovirus infection.

The invention provides the application of a small molecule compound XL888 in the preparation of a drug for treating adenovirus infection, and provides a safe and effective small molecule compound for the clinical treatment of adenovirus. XL888 can effectively inhibit the replication of adenovirus within a non-toxic range, and can be further developed as a drug for treating diseases caused by adenovirus infection, and has broad application prospects.

The XL888 of the present invention is a small molecular compound, and it has no cytotoxicity at 5 μM in Vero cells. Therefore, the _CC50 (lethal concentration in half) is greater than 5 μM. XL888 can dose-dependently inhibit virus replication for both adenoviruses (AdV3 and AdV5). Its IC ₅₀ (half inhibitory concentration) against AdV3 in Vero cells is only 0.17 μM, and its IC ₅₀ against AdV5 is 0.48 μM. By calculation, the selection index (SI) of XL888 is greater than 10 on both adenoviruses, indicating that XL888 has a broad spectrum of anti-adenovirus complexes.

The present invention provides a novel anti-adenovirus drug-XL888, which makes up for the technical defect that there is no anti-viral drug for adenovirus infection in the prior art.

The XL888 of the present invention, as a novel antitumor drug under development, is in phase I clinical trials and has a large amount of clinical safety experimental data. If its indications are extended to the treatment of adenovirus infection, the risk of failure in clinical safety trials can be significantly reduced, and the time and cost of new drug development can be greatly saved.

As auxiliary evidence of the inventiveness of the claims of the present invention, it is also reflected in the following important aspects:

The expected benefits and commercial value after the transformation of the technical solution of the present invention are: the present invention is oriented to meet clinical needs, focuses on the core therapeutic field, is based on clinical value, pharmacoeconomic value, and commercial value of the product, and has huge commercial value and The expected return after conversion. The technical solution of the present invention fills up the technological gap in the industry at home and abroad: the present invention provides a new technology of antiviral drugs for adenovirus infection.

Description of drawings

Fig. 1 is a schematic diagram of the cell viability of Vero cells measured relative to cells without drug treatment after Vero cells provided by the embodiment of the present invention and XL888 with different concentration gradients were incubated for 48 hours at 37°C in an incubator containing 5% CO ₂ ;

Figure 2 is the Vero cells provided by the embodiment of the present invention, which were added with different concentration gradients of XL888, infected with AdV3 at an MOI of 0.55, and incubated at 37°C for 48 hours. Schematic diagram of the percentage inhibition rate of AdV3;

Figure 3 is the Vero cells provided by the embodiment of the present invention with different concentration gradients of XL888 added, infected with AdV5 at an MOI of 1.1, and after incubation at 37°C for 48 hours, the Vero cells treated with different drug concentration gradients relative to the cells without drugs after virus infection Schematic diagram of the percentage inhibition rate against AdV5.

Detailed ways

In order to make the object, technical solution and advantages of the present invention more clear, the present invention will be further described in detail below in conjunction with the examples. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention.

1. Explain the embodiment. In order to make those skilled in the art fully understand how to implement the present invention, this part is an explanatory embodiment for explaining the technical solution of the claims.

The use of XL888 provided in the embodiment of the present invention in the preparation of medicaments and adenovirus inhibitors for alleviating and/or preventing and/or treating adenovirus infection.

The XL888 chemical structural formula that the embodiment of the present invention provides is as follows:

The adenovirus provided in the embodiment of the present invention can be any one or more of human adenovirus types 1, 3, 4, 5, 7, 11, 14, 40, 41 and 55.

The medicaments provided in the embodiments of the present invention for alleviating and/or preventing and/or treating adenovirus infection work by inhibiting the activity of adenovirus replication.

The medicament for alleviating and/or preventing and/or treating adenovirus infection provided by the embodiment of the present invention includes XL888 and a pharmaceutically acceptable carrier.

The dosage form of the drug for alleviating and/or preventing and/or treating adenovirus infection provided by the embodiments of the present invention is any clinically acceptable oral administration form, injection administration form or external administration dosage form.

The medicaments provided in the embodiments of the present invention for alleviating and/or preventing and/or treating adenovirus infection are tablets, capsules, granules, oral liquids, and injections.

2. Application examples. In order to prove the creativity and technical value of the technical solution of the present invention, this part is the application example of the claimed technical solution on specific products or related technologies.

The XL888 provided by the embodiments of the present invention is applied to the preparation of drugs and adenovirus inhibitors for alleviating and/or preventing and/or treating adenovirus infection. XL888 can effectively inhibit the replication of adenovirus within a non-toxic range, and can be further developed as a drug for treating diseases caused by adenovirus infection, and has broad application prospects. In view of the fact that there is no approved drug for the treatment of adenovirus infection, the present invention provides a new technology for the treatment of adenovirus infection.

3. Evidence of the relevant effects of the embodiment. The embodiment of the present invention has achieved some positive effects in the process of research and development or use, and indeed has great advantages compared with the prior art. The following content is described in conjunction with the data and charts of the test process.

The present invention detects the toxicity of XL888 to cells on the African green monkey kidney cell line Vero, and simultaneously measures the toxicity of XL888 to type 3 adenovirus (AdV3) and type 5 adenovirus (AdV5) in the Vero cell line. Inhibitory effect of adenovirus. The results showed that the small molecule compound XL888 had significant dose-dependent anti-adenovirus activity against both AdV3 and AdV5. Therefore, XL888 of the present invention is a novel antiviral drug against adenovirus, which has the advantages of good safety, high selectivity index and broad-spectrum anti-adenovirus, etc. It can be used to develop drugs for the treatment of adenovirus infection and has wide applications prospect.

1. Experimental materials:

(1) Cell lines, experimental animals and viruses required for the experiment

Vero cells were purchased from the American Type Culture Collection (ATCC);

Strains used: type B adenovirus AdV3, type C adenovirus AdV5.

Drugs required for the experiment: XL888 was purchased from Selleck Chemicals; for cell experiments, the drug was dissolved with DMSO.

Reagents required for the experiment:

DMEM medium and fetal bovine serum (FBS) were purchased from GIBCO;

CellTiter-Glo Cell Proliferation Detection Kit was purchased from Promega.

(2) Instruments required for the experiment

EnSpire multifunctional microplate reader was purchased from PerkinElmer;

The _CO2 cell culture box was purchased from Thermo Company;

The Operetta CLS high-content imaging analysis system was purchased from PerkinElmer.

2. Experimental method

2.1 The cytotoxicity test of XL888 is as follows:

(1) The vero cell line Vero was plated in a 96-well plate at 2×10 ⁴ per well, and cultured for 24 hours.

(2) Add XL888 diluted with medium to different gradient concentrations, and continue culturing for 48 hours in an incubator containing 5% CO ₂ at 37°C.

(3) Detecting the cell viability after treatment with different concentrations of drugs to detect the cytotoxicity of XL888.

(4) Use Graphpad to plot the logarithm of the relative cell viability (Cell viability) of the drug concentration, and calculate the half cytotoxic concentration (CC ₅₀ ) of the drug.

2.2 Evaluation of the antiviral activity of XL888 against adenovirus AdV3 in a cell model includes:

(1) The vero cell line Vero was plated in a 96-well plate at 2×10 ⁴ per well, and cultured for 24 hours. In order to detect its antiviral efficacy, Vero cells were infected with adenovirus AdV3 at MOI (multiplicity of infection) of 0.55.

(2) At the same time, add XL888 diluted with medium to different gradient concentrations, and continue culturing for 48 hours in an incubator containing 5% CO ₂ at 37°C.

(3) Use indirect immunofluorescence assay (Indirect immunofluorescence assay, IFA) to detect the number of positive cells infected with virus (Hexon positive cells) in the cell wells of the drug treatment group and the untreated group, in order to evaluate the adenovirus AdV3 after different concentrations of XL888 treatment. level of replication.

(4) Use Graphpad to plot the logarithm of the inhibition rate (Inhibition rate) against the drug concentration, and calculate the half inhibitory concentration (IC ₅₀ ) of the drug against the adenovirus AdV3. The selection index of XL888 on Vero cell line to adenovirus AdV3 was calculated.

2.3 Evaluate the antiviral activity of XL888 against adenovirus AdV5 in a cell model as follows:

1) The vero cell line Vero was plated in a 96-well plate at 2×10 ⁴ per well, and cultured for 24 hours. In order to detect its antiviral effect, Vero cells were infected with adenovirus AdV5 at an MOI (multiplicity of infection) of 1.1.

2) At the same time, add XL888 diluted to different gradient concentrations with culture medium, and continue culturing for 48 hours in an incubator containing 5% CO ₂ at 37°C.

3) Indirect immunofluorescence assay (Indirect immunofluorescence assay, IFA) was used to detect the number of positive cells infected with virus (Hexon positive cells) in the cell wells of the drug treatment group and the untreated group, in order to evaluate the expression of adenovirus AdV5 after different concentrations of XL888 treatment. copy level.

4) Use Graphpad to plot the logarithm of the inhibition rate (Inhibition rate) against the drug concentration, and calculate the half inhibitory concentration (IC ₅₀ ) of the drug against the adenovirus AdV5. The selection index of XL888 on Vero cell line to adenovirus AdV5 was calculated.

2.4 Evaluation of cytotoxicity of XL888 in Vero cell line

(1) Cell culture

After 2 subcultures, the frozen and revived cells were cultured in DMEM medium containing 10% fetal bovine serum and double antibodies (penicillin 100 U/ml, streptomycin 100 μg/ml), and the seeding density was not lower than 1×10 ⁴ cell/ml, the passage density is not higher than 5x10 ⁴ cell/ml.

(2) Drug treatment of cells

Vero cells were inoculated in a 96-well cell culture plate at 1×10 ⁴ cells/well (volume 100 μL), cultured for 24 h until the confluence of the cell wells reached 80%; Double antibody) to prepare drugs, and add to the corresponding cell wells and mix well. Set up 6 concentration gradients for the drug, and set up 2 duplicate wells for each gradient concentration, with the final concentrations of 0.02 μM, 0.06 μM, 0.19 μM, 0.56 μM, 1.67 μM and 5 μM, in an incubator containing 5% _CO2 at 37°C Continue culturing for 48 h.

(3) Calculate the toxicity of the drug to the cells in each detection well

试剂，将板在室温下孵育10分钟以稳定发光信号。用EnSpire酶标仪检测化学发光读数，计算细胞存活率。Remove the supernatant and add 100 μL CellTiter-

Reagents, incubate the plate at room temperature for 10 minutes to stabilize the luminescent signal. Chemiluminescent readings were detected with an EnSpire microplate reader, and cell viability was calculated.

Cell survival rate (%)=drug treatment group/untreated control group*100%

The results are shown in Figure 1. After treatment of Vero cells with XL888 at the highest concentration of 5 μM for 48 hours, the cell viability was slightly different from that of the control group, indicating that XL888 had weak toxicity to cells at this concentration, and its half-toxicity concentration _CC50 was greater than 5 μM.

2.5 Evaluation of the anti-AdV3 adenovirus activity of XL888 in Vero cell line

(1) Cell culture

After 2 subcultures, the frozen and revived cells were cultured in DMEM medium containing 10% fetal bovine serum and double antibodies (penicillin 100 U/ml, streptomycin 100 μg/ml), and the seeding density was not lower than 1×10 ⁴ cell/ml, the passage density is not higher than 5x10 ⁴ cell/ml.

(2) Drug treatment of cells

Vero cells were inoculated in a 96-well cell culture plate at 1×10 ⁴ cells/well (volume 100 μL), and cultured for 24 hours until the confluence of the cell wells reached 80%; the infection group was added with 0.55 MOI (multiplicity of infection) of AdV3 virus, and at the same time, each Gradient concentration of the drug (starting at 5 μM, serial 3-fold serial dilution of 6 gradients, two duplicate wells for each gradient) to a total volume of 200 μL of culture medium (DMEM medium + 2% serum + double antibody), in the cell Incubate for 48 hours at 37°C in an incubator.

(3) Detection of specific fluorescently labeled viruses by indirect immunofluorescence

CLS^TM高内涵分析系统观察样品，然后拍摄并分析图像。Cell culture plates were washed twice with cells in PBS and fixed with 4% paraformaldehyde (4% PFA in PBS) for 20 minutes at room temperature. Fixed samples were washed 3 times with PBST (0.05% tween 20 in PBS) and then incubated in blocking buffer (3% BSA, 0.3% Triton X-100 and 10% FBS in PBS) for 1 hour at room temperature. It was then incubated overnight at 4° C. in binding buffer (3% BSA, 0.3% TritonX-100 in PBS) of a mouse monoclonal antibody against the adenoviral viral hexon protein (dilution 1:200). After 3 washes with PBST, samples were incubated in binding buffer with goat FITC-conjugated anti-mouse secondary antibody (dilution 1:1000) and DAPI (dilution 1:10000) for 1 hour at room temperature in the dark . After rinsing 3 times with PBST, use

The CLS ^TM high-content analysis system observes the sample, then captures and analyzes the images.

(4) Calculate the inhibitory rate of the drug to the virus in each detection hole

Cells are marked by DAPI staining, and FITC staining intensity represents the level of viral replication. FITC background fluorescence values were measured in uninfected control cells. Cells with FITC intensity three times higher than control cells were defined as positive cells for adenovirus infection. Calculate the ratio of adenovirus-infected positive cells in the total cells.

Inhibition rate (%)=100%-(drug treatment well-blank control)/(virus control well-blank control)*100%

The results are shown in Figure 2, XL888 significantly inhibited the replication of adenovirus AdV3 in a dose-dependent manner, and its half effective concentration IC ₅₀ was 0.17 μM.

(5) Calculation of drug selection index

The drug selection index (SI) is used to judge the safe range of the drug effect, and the selection index is greater than 3 to be effective, and the larger the index, the larger the safe range. Its calculation formula is: SI=CC ₅₀ /IC ₅₀

Combined with the above data, the selection index of XL888 on Vero for adenovirus AdV3 is greater than 10, and it has effective anti-adenovirus AdV3 activity.

2.6 Evaluation of the anti-AdV5 adenovirus activity of XL888 in Vero cell line

(1) Cell culture

After 2 subcultures, the frozen and revived cells were cultured in DMEM medium containing 10% fetal bovine serum and double antibodies (penicillin 100 U/ml, streptomycin 100 μg/ml), and the seeding density was not lower than 1×10 ⁴ cell/ml, the passage density is not higher than 5x10 ⁴ cell/ml.

(2) Drug treatment of cells

Vero cells were inoculated in a 96-well cell culture plate at 1×10 ⁴ cells/well (volume 100 μL), and cultured for 24 hours until the confluence of the cell wells reached 80%; the infection group was added with 1.1 MOI (multiplicity of infection) of AdV5 virus, and at the same time, each Gradient concentration of the drug (starting at 5 μM, serial 3-fold serial dilution of 6 gradients, two duplicate wells for each gradient) to a total volume of 200 μL of culture medium (DMEM medium + 2% serum + double antibody), in the cell Incubate for 48 hours at 37°C in an incubator.

(3) Detection of specific fluorescently labeled viruses by indirect immunofluorescence

CLS^TM高内涵分析系统观察样品，然后拍摄并分析图像。Cell culture plates were washed twice with cells in PBS and fixed with 4% paraformaldehyde (4% PFA in PBS) for 20 minutes at room temperature. Fixed samples were washed 3 times with PBST (0.05% tween 20 in PBS) and then incubated in blocking buffer (3% BSA, 0.3% Triton X-100 and 10% FBS in PBS) for 1 hour at room temperature. It was then incubated overnight at 4° C. in binding buffer (3% BSA, 0.3% TritonX-100 in PBS) of a mouse monoclonal antibody against the adenoviral viral hexon protein (dilution 1:200). After 3 washes with PBST, samples were incubated in binding buffer with goat FITC-conjugated anti-mouse secondary antibody (dilution 1:1000) and DAPI (dilution 1:10000) for 1 hour at room temperature in the dark . After rinsing 3 times with PBST, use

The CLS ^TM high-content analysis system observes the sample, then captures and analyzes the images.

(4) Calculate the inhibitory rate of the drug to the virus in each detection hole

Cells are marked by DAPI staining, and FITC staining intensity represents the level of viral replication. FITC background fluorescence values were measured in uninfected control cells. Cells with FITC intensity three times higher than control cells were defined as positive cells for adenovirus infection. Calculate the ratio of adenovirus-infected positive cells in the total cells.

Inhibition rate (%)=100%-(drug treatment well-blank control)/(virus control well-blank control)*100%

The results are shown in Figure 3, XL888 significantly inhibited the replication of adenovirus AdV5 in a dose-dependent manner, and its half effective concentration IC ₅₀ was 0.48 μM.

(5) Calculation of drug selection index

The drug selection index (SI) is used to judge the safe range of the drug effect, and the selection index is greater than 3 to be effective, and the larger the index, the larger the safe range. Its calculation formula is: SI=CC ₅₀ /IC ₅₀

Combined with the above data, the selection index of XL888 on Vero for adenovirus AdV5 is greater than 10, and it has effective anti-adenovirus AdV5 activity.

The above is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Anyone familiar with the technical field within the technical scope disclosed in the present invention, whoever is within the spirit and principles of the present invention Any modifications, equivalent replacements and improvements made within shall fall within the protection scope of the present invention.

Claims (7)

1. Use of XL888 for the preparation of a medicament for the alleviation and/or prevention and/or treatment of adenoviral infections;

the medicament for relieving and/or preventing and/or treating the adenovirus infection comprises XL888 and a pharmaceutically acceptable carrier.

2. The use according to claim 1, wherein the adenovirus is one or more of adenovirus type 1, 3, 4, 5, 7, 11, 14, 40, 41 and 55.

3. The use according to claim 1, wherein the adenovirus comprises a group B adenovirus AdV3 subtype, a group C adenovirus AdV5 subtype.

4. The use according to claim 1, wherein the adenovirus infection is one or more of a respiratory disease, an intestinal disease, and a corneal disease.

5. The use according to claim 1, wherein the medicament for alleviating and/or preventing and/or treating adenovirus infection is in any one of clinically acceptable oral administration dosage forms or injection administration dosage forms.

6. The use according to claim 1, wherein the medicament for alleviating and/or preventing and/or treating adenovirus infection is in any clinically acceptable form for external administration.

7. The use according to claim 1, wherein the medicament for alleviating and/or preventing and/or treating adenovirus infection is a tablet, a capsule, a granule, an oral liquid, an injection.

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