Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease
Copyright policy )Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease
AbstractCOVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (Mpro, also called 3CLpro) is essential for processing and maturation of the viral polyprotein, therefore recognized as an attractive drug target. Here we show that a clinically approved anti-HCV drug, Boceprevir, and a pre-clinical inhibitor against feline infectious peritonitis (corona) virus (FIPV), GC376, both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting Mpro. Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect. Further structural analysis reveals binding of both inhibitors to the catalytically active side of SARS-CoV-2 protease Mpro as main mechanism of inhibition. Our findings may provide critical information for the optimization and design of more potent inhibitors against the emerging SARS-CoV-2 virus.
- Shanghai Synchrotron Radiation Facility China (People's Republic of)
- Universidad de Bogotá Jorge Tadeo Lozano Colombia
- Chinese Academy of Science (中国科学院) China (People's Republic of)
- Chinese Academy of Science China (People's Republic of)
- Chinese Academy of Sciences China (People's Republic of)
Models, Molecular, Pyrrolidines, General Physics and Astronomy, Infectious disease (medical specialty), FOS: Health sciences, Crystallography, X-Ray, Biochemistry, Telaprevir, Catalytic Domain, Chlorocebus aethiops, Pathology, Disease, Coronavirus 3C Proteases, Boceprevir, Hepatitis C virus, Q, Virus, Cysteine Endopeptidases, Chemistry, Infectious Diseases, Computational Theory and Mathematics, Physical Sciences, Medicine, Coronavirus Infections, Computational Methods in Drug Discovery, Proline, Science, Pneumonia, Viral, Coronavirus Disease 2019 Research, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, Síndrome respiratorio agudo grave, Virology, Health Sciences, Ribavirin, Animals, Protease Inhibitors, Pandemics, Biology, Binding Sites, Corona Virus, SARS-CoV-2, Vero cell, COVID-19, Gastrointestinal Viral Infections and Vaccines Development, General Chemistry, RNA-Dependent RNA Polymerase, High-Throughput Screening Assays, Protease, Coronavirus, Coronavirus disease 2019 (COVID-19), Disease Models, Animal, Enzyme, Computer Science
Models, Molecular, Pyrrolidines, General Physics and Astronomy, Infectious disease (medical specialty), FOS: Health sciences, Crystallography, X-Ray, Biochemistry, Telaprevir, Catalytic Domain, Chlorocebus aethiops, Pathology, Disease, Coronavirus 3C Proteases, Boceprevir, Hepatitis C virus, Q, Virus, Cysteine Endopeptidases, Chemistry, Infectious Diseases, Computational Theory and Mathematics, Physical Sciences, Medicine, Coronavirus Infections, Computational Methods in Drug Discovery, Proline, Science, Pneumonia, Viral, Coronavirus Disease 2019 Research, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, Síndrome respiratorio agudo grave, Virology, Health Sciences, Ribavirin, Animals, Protease Inhibitors, Pandemics, Biology, Binding Sites, Corona Virus, SARS-CoV-2, Vero cell, COVID-19, Gastrointestinal Viral Infections and Vaccines Development, General Chemistry, RNA-Dependent RNA Polymerase, High-Throughput Screening Assays, Protease, Coronavirus, Coronavirus disease 2019 (COVID-19), Disease Models, Animal, Enzyme, Computer Science
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