期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 21, 期 10, 页码 3088-3091出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.03.034
关键词
3CL Protease; Severe acute respiratory syndrome; SARS; Coronavirus; FRET-based assays; Autodock; Virtual screening; Grid
资金
- Ministry of Knowledge Economy (MKE), South Korea
The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308 307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environment. The top 1468 ranked compounds with free binding energy ranging from -14.0 to -17.09 kcal mol(-1) were selected to check the hydrogen bond interaction with amino acid residues in the active site of 3CL(pro). Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CL(pro) expressed by Escherichia coli. Seven of the 53 compounds were selected; their IC(50) ranged from 38.57 +/- 2.41 to 101.38 +/- 3.27 mu M. Two strong 3CL(pro) inhibitors were further identified as competitive inhibitors of 3CL(pro) with K(i) values of 9.11 +/- 1.6 and 9.93 +/- 0.44 mu M. Hydrophobic and hydrogen bond interactions of compound with amino acid residues in the active site of 3CL(pro) were also identified. (C) 2011 Elsevier Ltd. All rights reserved.
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