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Bioorganic & Medicinal Chemistry Letters / Bioorganic and Medicinal Chemistry Letters 21 (2011) 3088-3091
Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation
H.-J. Ryu, S.-H. Lee, S. Hwang, V. Breton1, J. H. Rhee, D. Kim

The 3C-like protease (3CLpro) 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 3CLpro. Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CLpro expressed by Escherichia coli. Seven of the 53 compounds were selected; their IC50 ranged from 38.57 ± 2.41 to 101.38 ± 3.27 muM. Two strong 3CLpro inhibitors were further identified as competitive inhibitors of 3CLpro with Ki values of 9.11 ± 1.6 and 9.93 ± 0.44 muM. Hydrophobic and hydrogen bond interactions of compound with amino acid residues in the active site of 3CLpro were also identified.
1 :  LPC - Laboratoire de Physique Corpusculaire [Clermont-Ferrand]

Sciences du Vivant/Bio-Informatique, Biologie Systémique
3CL Protease – Severe acute respiratory syndrome – SARS – Coronavirus – FRET-based assays – Autodock – Virtual screening – Grid