Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies

J Med Chem. 2006 Jun 15;49(12):3485-95. doi: 10.1021/jm050852f.


The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) 3C-like protease (3CL(pro) or M(pro)) is an attractive target for the development of anti-SARS drugs because of its crucial role in the viral life cycle. In this study, a compound database was screened by the structure-based virtual screening approach to identify initial hits as inhibitors of SARS-CoV 3CL(pro). Out of the 59,363 compounds docked, 93 were selected for the inhibition assay, and 21 showed inhibition against SARS-CoV 3CL(pro) (IC(50) <or= 30 microM), with three of them having common substructures. Furthermore, a search for analogues with common substructure in the Maybridge, ChemBridge, and SPECS_SC databases led to the identification of another 25 compounds that exhibited inhibition against SARS-CoV 3CL(pro) (IC(50) = 3-1,000 microM). These compounds, 28 in total, were subjected to 3D-QSAR studies to elucidate the pharmacophore of SARS-CoV 3CL(pro).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Coronavirus 3C Proteases
  • Cysteine Endopeptidases / chemistry*
  • Models, Molecular*
  • Oligopeptides / chemistry
  • Protease Inhibitors / chemistry*
  • Quantitative Structure-Activity Relationship*
  • Severe acute respiratory syndrome-related coronavirus / enzymology*
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry*


  • Oligopeptides
  • Protease Inhibitors
  • Viral Proteins
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases