title: Discovery of a novel family of SARS-CoV protease inhibitors by virtual screening and 3D-QSAR studies.
abstract: 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).
authors.affiliation: Department of Life Science, Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300, Taiwan, Republic of China.
authors.forename: Keng-Chang
authors.initials: KC
authors.lastname: Tsai
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Chen
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Liang
authors.forename: I-Lin
authors.initials: IL
authors.lastname: Lu
authors.forename: Neeraj
authors.initials: N
authors.lastname: Mahindroo
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Lincoln
authors.initials: L
authors.lastname: Liu
authors.forename: Donald
authors.initials: D
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Lien
authors.forename: Thy-Hou
authors.initials: TH
authors.lastname: Lin
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wu
mesh_terms: D001665:Binding Sites; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases