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; Vincent Breton; J. H. Rhee; D. Kim

doi:10.1016/j.bmcl.2011.03.034

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 Vincent Breton ¹ J. H. Rhee D. Kim

1 LPC - Laboratoire de Physique Corpusculaire - Clermont-Ferrand

Abstract : 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.

Keywords : 3CL Protease Severe acute respiratory syndrome SARS Coronavirus FRET-based assays Autodock Virtual screening Grid

Type de document :

Article dans une revue

Bioorganic and Medicinal Chemistry Letters, Elsevier, 2011, 21, pp.3088-3091. <10.1016/j.bmcl.2011.03.034>

Domaine :

Informatique [cs] / Bio-informatique [q-bio.QM]

Sciences du Vivant [q-bio] / Bio-Informatique, Biologie Systémique [q-bio.QM]

Liste complète des métadonnées

http://hal.in2p3.fr/in2p3-00586373
Contributeur : Jeanine Pellet <>
Soumis le : vendredi 15 avril 2011 - 16:12:29
Dernière modification le : mercredi 23 novembre 2011 - 14:02:40

Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation

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