Chem. J. Chinese Universities

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Interactions of [Mo6O19]2- and Its Derivatives Substituted with Organic Groups Inhibitor with SARS-CoV 3CLpro by Molecular Modeling

SHAO Chen1, WANG Jian-Ping1, YANG Guo-Chun1, SU Zhong-Min1,2*, HU Dong-Hua1, SUN Chia-Chung2   

    1. Institute of Functional Material Chemistry, Northeast Normal University, Changchun 130024, China;
    2. State Key Laboratory of Theoretical and Computational Chemistry, Jilin University, Changchun 130021, China
  • Received:2006-09-06 Revised:1900-01-01 Online:2008-01-10 Published:2008-01-10
  • Contact: SU Zhong-Min

Abstract: Polyoxometalates(POMs) were proved with the properties of both anti-tumor and anti-HIV. The potential anti-SARS activities of the polyoxometalates [Mo6O19]2- and its derivatives substituted with organic groups were investigated in this paper by molecular modeling method. The 3c like(3CL)protease hydrolyze, namely 3CLpro, is the key protease for virus replication as well as transcription, and thus can be taken as one of the key targets for anti-SARS drug design. InsightII/Dicover 3, affinity, Profile-3D modules were used to explore possible binding locations and properties for POMs/3CLpro interaction. We studied the energy changing tend and investigated the possible inhibiting mechanism of POMs' with SARS-CoV. The results show that POMs bind with 3CLpro in the active site with a high affinity, mainly via electrostatic interactions and H-bond interactions. For the POMs/3CLpro complex, POMs substituted with organic groups with higher negative charge are prefer to bind with 3CLpro than non-substituted ones, and this agrees well with relative quantum chemical calculations. Organic substitutions in ligands have an influence on the stability of complexes by steric hindrance. Our study may provide theoretical reference and illustrations to anti SARS-CoV drug design.

Key words: SARS, 3CLpro, Polyoxometalate, Molecular dynamics, Docking

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