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  • Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease #MMPMID32887884
  • Fu L; Ye F; Feng Y; Yu F; Wang Q; Wu Y; Zhao C; Sun H; Huang B; Niu P; Song H; Shi Y; Li X; Tan W; Qi J; Gao GF
  • Nat Commun 2020[Sep]; 11 (1): 4417 PMID32887884show ga
  • COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (M(pro), 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 M(pro). 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 M(pro) 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.
  • |Animals[MESH]
  • |Antiviral Agents/pharmacology[MESH]
  • |Betacoronavirus/*drug effects/enzymology[MESH]
  • |Binding Sites/drug effects[MESH]
  • |COVID-19[MESH]
  • |Catalytic Domain[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Coronavirus 3C Proteases[MESH]
  • |Coronavirus Infections/*drug therapy/*virology[MESH]
  • |Crystallography, X-Ray[MESH]
  • |Cysteine Endopeptidases/chemistry/metabolism[MESH]
  • |Disease Models, Animal[MESH]
  • |High-Throughput Screening Assays[MESH]
  • |Models, Molecular[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*drug therapy/*virology[MESH]
  • |Proline/*analogs & derivatives/pharmacology[MESH]
  • |Protease Inhibitors/*pharmacology[MESH]
  • |Pyrrolidines/*pharmacology[MESH]
  • |RNA-Dependent RNA Polymerase/antagonists & inhibitors/chemistry/metabolism[MESH]
  • |SARS-CoV-2[MESH]
  • |Vero Cells[MESH]
  • |Viral Nonstructural Proteins/*antagonists & inhibitors/chemistry/metabolism[MESH]
  • |Virus Replication/drug effects[MESH]

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  • suck abstract from ncbi

    4417 1.11 2020