Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation - IN2P3 - Institut national de physique nucléaire et de physique des particules
Article Dans Une Revue Bioorganic and Medicinal Chemistry Letters Année : 2011

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

H.-J. Ryu
  • Fonction : Auteur
S.-H. Lee
  • Fonction : Auteur
S. Hwang
  • Fonction : Auteur
J. H. Rhee
  • Fonction : Auteur
D. Kim
  • Fonction : Auteur

Résumé

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.

Dates et versions

in2p3-00586373 , version 1 (15-04-2011)

Identifiants

Citer

H.-J. Ryu, S.-H. Lee, S. Hwang, Vincent Breton, J. H. Rhee, et al.. Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation. Bioorganic and Medicinal Chemistry Letters, 2011, 21, pp.3088-3091. ⟨10.1016/j.bmcl.2011.03.034⟩. ⟨in2p3-00586373⟩
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