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

Keng Chang Tsai, Shih Yuan Chen, Po Huang Liang, I. Lin Lu, Neeraj Mahindroo, Hsing Pang Hsieh, Yu Sheng Chao, Lincoln Liu, Donald Liu, Wei Lien, Thy Hou Lin, Su Ying Wu

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) 3C-like protease (3CLpro or Mpro) 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 3CLpro. Out of the 59 363 compounds docked, 93 were selected for the inhibition assay, and 21 showed inhibition against SARS-CoV 3CLpro (IC50 ≤ 30 μM), 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 3CLpro (IC50 = 3-1000 μM). These compounds, 28 in total, were subjected to 3D-QSAR studies to elucidate the pharmacophore of SARS-CoV 3CLpro.

Original languageEnglish
Pages (from-to)3485-3495
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number12
Publication statusPublished - 2006 Jun 15

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery


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