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  • Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication #MMPMID32855413
  • Vuong W; Khan MB; Fischer C; Arutyunova E; Lamer T; Shields J; Saffran HA; McKay RT; van Belkum MJ; Joyce MA; Young HS; Tyrrell DL; Vederas JC; Lemieux MJ
  • Nat Commun 2020[Aug]; 11 (1): 4282 PMID32855413show ga
  • The main protease, M(pro) (or 3CL(pro)) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor. Here, we show the prodrug and its parent GC373, are effective inhibitors of the M(pro) from both SARS-CoV and SARS-CoV-2 with IC50 values in the nanomolar range. Crystal structures of SARS-CoV-2 M(pro) with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals. The work here lays the framework for their use in human trials for the treatment of COVID-19.
  • |A549 Cells[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/chemistry/*pharmacology[MESH]
  • |Betacoronavirus/*drug effects/enzymology[MESH]
  • |Binding Sites[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Coronavirus 3C Proteases[MESH]
  • |Coronavirus, Feline/*drug effects/enzymology[MESH]
  • |Crystallography, X-Ray[MESH]
  • |Cysteine Endopeptidases/chemistry[MESH]
  • |Cytopathogenic Effect, Viral/drug effects[MESH]
  • |Drug Repositioning[MESH]
  • |Humans[MESH]
  • |Inhibitory Concentration 50[MESH]
  • |Molecular Structure[MESH]
  • |Prodrugs[MESH]
  • |Protease Inhibitors/chemistry/*pharmacology[MESH]
  • |Pyrrolidines/chemistry/pharmacology[MESH]
  • |SARS Virus/drug effects/enzymology[MESH]
  • |SARS-CoV-2[MESH]
  • |Vero Cells[MESH]
  • |Viral Nonstructural Proteins/*antagonists & inhibitors/chemistry[MESH]
  • |Virus Replication/drug effects[MESH]

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  • suck abstract from ncbi

    4282 1.11 2020