Abstract
In order to find effective peptide inhibitors against SARS CoV Mpro, an analysis was performed for 11 oligopeptides that can be cleaved by the SARS coronavirus main protease (CoV Mpro, or 3CLpro). Flexible molecular alignments of the 11 cleavable peptides have provided useful insights into the chemical properties of their amino acid residues close to the cleavage site. Moreover, it was found through the ligand-receptor docking studies that of the 11 cleavable peptides, NH2-ATLQ↓AIAS-COOH and NH2-ATLQ↓AENV-COOH had the highest affinity with SARS CoV Mpro. The two octapeptides were selected as initial templates for further chemical modification to make them become effective inhibitors against the SARS enzyme according to the “distorted key” theory [K. C. Chou, Analytical Biochemistry 233 (1996) 1-14]. The possible chemical modification methods are proposed and examined. The approach developed in this study and the findings thus obtained might stimulate new strategies and provide useful information for drug design against SARS.
Keywords: SARS, CoV Mpro, protease inhibitor, cleavable peptides, rack mechanism, Chou's distorted key theory, bioinformatics
Medicinal Chemistry
Title: Inhibitor Design for SARS Coronavirus Main Protease Based on “Distorted Key Theory”
Volume: 3 Issue: 1
Author(s): Qi-Shi Du, Hao Sun and Kuo-Chen Chou
Affiliation:
Keywords: SARS, CoV Mpro, protease inhibitor, cleavable peptides, rack mechanism, Chou's distorted key theory, bioinformatics
Abstract: In order to find effective peptide inhibitors against SARS CoV Mpro, an analysis was performed for 11 oligopeptides that can be cleaved by the SARS coronavirus main protease (CoV Mpro, or 3CLpro). Flexible molecular alignments of the 11 cleavable peptides have provided useful insights into the chemical properties of their amino acid residues close to the cleavage site. Moreover, it was found through the ligand-receptor docking studies that of the 11 cleavable peptides, NH2-ATLQ↓AIAS-COOH and NH2-ATLQ↓AENV-COOH had the highest affinity with SARS CoV Mpro. The two octapeptides were selected as initial templates for further chemical modification to make them become effective inhibitors against the SARS enzyme according to the “distorted key” theory [K. C. Chou, Analytical Biochemistry 233 (1996) 1-14]. The possible chemical modification methods are proposed and examined. The approach developed in this study and the findings thus obtained might stimulate new strategies and provide useful information for drug design against SARS.
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Cite this article as:
Du Qi-Shi, Sun Hao and Chou Kuo-Chen, Inhibitor Design for SARS Coronavirus Main Protease Based on “Distorted Key Theory”, Medicinal Chemistry 2007; 3 (1) . https://dx.doi.org/10.2174/157340607779317616
DOI https://dx.doi.org/10.2174/157340607779317616 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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