SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances a... more SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here, we exploited the enormous potential of plant metabolism using the bryophyte Marchantia polymorpha L. and identified a potent SARS-CoV-2 antiviral, following a bioactivity-guided fractionation and mass-spectrometry approach. We found that the chlorophyll derivative Pheophorbide a (PheoA), a porphyrin compound similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2, preventing infection of cultured monkey and human cells, without noticeable cytotoxicity. We also show that PheoA targets the viral particle, interfering with its i...
Although their origin, nature and structure are not identical, a common feature of positive-stran... more Although their origin, nature and structure are not identical, a common feature of positive-strand RNA viruses is their ability to subvert host lipids and intracellular membranes to generate replication and assembly complexes. Recently, lipin1, a cellular enzyme that converts phosphatidic acid into diacylglycerol, has been implicated in the formation of the membranous web that hosts hepatitis C virus (HCV) replicase. In the liver, lipin1 cooperates with lipin2 to maintain glycerolipid homeostasis. We extended our previous study of the lipin family on HCV infection, by determining the impact of the lipin2 silencing on viral replication. Our data reveal that lipin2 silencing interferes with HCV virion secretion at late stages of the infection, without significantly affecting viral replication or assembly. Moreover, uninfected lipin2-, but not lipin1-deficient cells display alterations in mitochondrial and Golgi apparatus morphology, suggesting that lipin2 contributes to the maintenanc...
CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin... more CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous varia...
ABSTRACT The article presents the results of a study conducted on an assemblage of archeofaunal r... more ABSTRACT The article presents the results of a study conducted on an assemblage of archeofaunal remains from the Copaca 1 archeological site, located on the arid coast of Northern Chile. The site corresponds to an extensive shell midden that was used generally as an occupational site and specifically as a funerary one by specialized marine hunteregatherers exclusively during the Archaic period. The analysis of the faunal remains enabled a general description of the use of local fauna throughout the site's cultural sequence, which range from 7866 to 5040 cal. BP. According to the results obtained, marine and terrestrial fauna, including marine and terrestrial mammals, sea birds, pelagic and oceanic fish, mollusks, crustaceans and equinoderms, were used as a source of both food and technological implements during the Middle Holocene. This implies that the human groups that inhabited Copaca 1 accessed most of the ecoanthropic spheres of the Southern Cone of the Southwestern Pacific coast from early times onward, an adaptation dated since 12,000 BP in the south-western coast from southern Peru and northern Chile
SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances a... more SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here, we exploited the enormous potential of plant metabolism using the bryophyte Marchantia polymorpha L. and identified a potent SARS-CoV-2 antiviral, following a bioactivity-guided fractionation and mass-spectrometry approach. We found that the chlorophyll derivative Pheophorbide a (PheoA), a porphyrin compound similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2, preventing infection of cultured monkey and human cells, without noticeable cytotoxicity. We also show that PheoA targets the viral particle, interfering with its i...
Although their origin, nature and structure are not identical, a common feature of positive-stran... more Although their origin, nature and structure are not identical, a common feature of positive-strand RNA viruses is their ability to subvert host lipids and intracellular membranes to generate replication and assembly complexes. Recently, lipin1, a cellular enzyme that converts phosphatidic acid into diacylglycerol, has been implicated in the formation of the membranous web that hosts hepatitis C virus (HCV) replicase. In the liver, lipin1 cooperates with lipin2 to maintain glycerolipid homeostasis. We extended our previous study of the lipin family on HCV infection, by determining the impact of the lipin2 silencing on viral replication. Our data reveal that lipin2 silencing interferes with HCV virion secretion at late stages of the infection, without significantly affecting viral replication or assembly. Moreover, uninfected lipin2-, but not lipin1-deficient cells display alterations in mitochondrial and Golgi apparatus morphology, suggesting that lipin2 contributes to the maintenanc...
CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin... more CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous varia...
ABSTRACT The article presents the results of a study conducted on an assemblage of archeofaunal r... more ABSTRACT The article presents the results of a study conducted on an assemblage of archeofaunal remains from the Copaca 1 archeological site, located on the arid coast of Northern Chile. The site corresponds to an extensive shell midden that was used generally as an occupational site and specifically as a funerary one by specialized marine hunteregatherers exclusively during the Archaic period. The analysis of the faunal remains enabled a general description of the use of local fauna throughout the site's cultural sequence, which range from 7866 to 5040 cal. BP. According to the results obtained, marine and terrestrial fauna, including marine and terrestrial mammals, sea birds, pelagic and oceanic fish, mollusks, crustaceans and equinoderms, were used as a source of both food and technological implements during the Middle Holocene. This implies that the human groups that inhabited Copaca 1 accessed most of the ecoanthropic spheres of the Southern Cone of the Southwestern Pacific coast from early times onward, an adaptation dated since 12,000 BP in the south-western coast from southern Peru and northern Chile
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