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 3CL^pro, 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/3CL^pro 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 3CL^pro in the active site with a high affinity, mainly via electrostatic interactions and H-bond interactions. For the POMs/3CL^pro complex, POMs substituted with organic groups with higher negative charge are prefer to bind with 3CL^pro 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, 3CL^pro, Polyoxometalate, Molecular dynamics, Docking