Progress in Computational Approach to Drug Development Against SARS

Kuo-Chen      Chou; Dong-Qing      Wei; Qi-Shi      Du; Suzanne      Sirois; Wei-Zhu      Zhong

Abstract

Since the outbreak of SARS (severe acute respiratory syndrome) in November 2002 in Southern Chinas Guangdong Province, considerable progress has been made in the development of drugs for SARS therapy. The present mini review is focused on the area of computer-aided drug discovery, i.e., the advances achieved mainly from the approaches of structural bioinformatics, pharmacophore modeling, molecular docking, peptide-cleavage site prediction, and other computational means. It is highlighted that the compounds C28H34O4N7Cl, C21H36O5N6 and C21H36O5N6 (Wei et al., Amino Acids, 2006, 31: 73-80), as well as KZ7088 (Chou et al. Biochem. Biophys. Res. Commun., 2003, 308: 148-151), a derivative of AG7088, might be the promising candidates for further investigation, and that the octapeptides ATLQAIAS and ATLQAENV, as well as AVLQSGFR, might be converted to effective inhibitors against the SARS enzyme. Meanwhile, how to modify these octapeptides based on the “distorted key” theory to make them become potent inhibitors is explicitly elucidated. Finally, a brief introduction is given for how to use computer-generated graphs to rapidly diagnose SARS coronavirus.

Keywords: SARS, Coronavirus proteinase, KZ7088, AG7088, Binding pocket, Octapeptide substrate, “distorted key” mechanism

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