Studies on the interactions of Ti-containing polyoxometalates (POMs) with SARS-CoV 3CL(pro) by molecular modeling

Ti-containing alpha-Keggin polyoxometalates (POMs) have been proved with properties of both anti-tumor and anti-HIV (human immunodeficiency virus). The potential anti-SARS (severe acute respiratory syndrome) activity of the POMs [alpha-PTi2W10O40](7-) isomers was investigated in this paper by molecular modeling method. The SARS 3c like protease, namely the SARS 3CL(pro) is the key function protease for virus replication as well as transcription and thus can be taken as one of the key targets for anti-SARS drug design. Affinity/Insight II was used to explore possible binding locations for POMs/3CL(pro) interaction. Charges in the POMs were obtained from density-functional theory (DFT) method. The results show that POMs bind with 3CL(pro) in the active site region with high affinity; POMs are more prone to bind with 3CL(pro) than with some organic compounds; for the POMs/3CL(pro) complex, the OTi2 in POMs is the vital element for electrostatic interaction, and the electrostatic binding energy is strong enough to keep the complex stable. (c) 2006 Elsevier Inc. All rights reserved.