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10.1128/AAC.00872-20

http://scihub22266oqcxt.onion/10.1128/AAC.00872-20
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32669265!7449189!32669265
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suck abstract from ncbi


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pmid32669265      Antimicrob+Agents+Chemother 2020 ; 64 (9): ä
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  • Discovery of M Protease Inhibitors Encoded by SARS-CoV-2 #MMPMID32669265
  • Hung HC; Ke YY; Huang SY; Huang PN; Kung YA; Chang TY; Yen KJ; Peng TT; Chang SE; Huang CT; Tsai YR; Wu SH; Lee SJ; Lin JH; Liu BS; Sung WC; Shih SR; Chen CT; Hsu JT
  • Antimicrob Agents Chemother 2020[Aug]; 64 (9): ä PMID32669265show ga
  • The coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is a health threat worldwide. Viral main protease (M(pro), also called 3C-like protease [3CL(pro)]) is a therapeutic target for drug discovery. Herein, we report that GC376, a broad-spectrum inhibitor targeting M(pro) in the picornavirus-like supercluster, is a potent inhibitor for the M(pro) encoded by SARS-CoV-2, with a half-maximum inhibitory concentration (IC(50)) of 26.4 +/- 1.1 nM. In this study, we also show that GC376 inhibits SARS-CoV-2 replication with a half-maximum effective concentration (EC(50)) of 0.91 +/- 0.03 muM. Only a small portion of SARS-CoV-2 M(pro) was covalently modified in the excess of GC376 as evaluated by mass spectrometry analysis, indicating that improved inhibitors are needed. Subsequently, molecular docking analysis revealed that the recognition and binding groups of GC376 within the active site of SARS-CoV-2 M(pro) provide important new information for the optimization of GC376. Given that sufficient safety and efficacy data are available for GC376 as an investigational veterinary drug, expedited development of GC376, or its optimized analogues, for treatment of SARS-CoV-2 infection in human is recommended.
  • |Amino Acid Motifs[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*chemistry/pharmacology[MESH]
  • |Betacoronavirus/*drug effects/pathogenicity[MESH]
  • |Catalytic Domain[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Coronavirus 3C Proteases[MESH]
  • |Cysteine Endopeptidases/*chemistry/genetics/metabolism[MESH]
  • |Gene Expression[MESH]
  • |Molecular Docking Simulation[MESH]
  • |Protease Inhibitors/*chemistry/pharmacology[MESH]
  • |Protein Binding[MESH]
  • |Protein Conformation, alpha-Helical[MESH]
  • |Protein Conformation, beta-Strand[MESH]
  • |Protein Interaction Domains and Motifs[MESH]
  • |Pyrrolidines/*chemistry/pharmacology[MESH]
  • |Recombinant Proteins/chemistry/genetics/metabolism[MESH]
  • |SARS-CoV-2[MESH]
  • |Sulfonic Acids[MESH]
  • |Thermodynamics[MESH]
  • |Vero Cells[MESH]
  • |Viral Nonstructural Proteins/antagonists & inhibitors/*chemistry/genetics/metabolism[MESH]


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