Abstract
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 language | English |
---|---|
Pages (from-to) | 3485-3495 |
Number of pages | 11 |
Journal | Journal of Medicinal Chemistry |
Volume | 49 |
Issue number | 12 |
DOIs | |
Publication status | Published - 2006 Jun 15 |
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery