title: Inhibitor design for SARS coronavirus main protease based on "distorted key theory".
abstract: In order to find effective peptide inhibitors against SARS CoV M(pro), an analysis was performed for 11 oligo-peptides that can be cleaved by the SARS coronavirus main protease (CoV M(pro), or 3CL(pro)). 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 M(pro). 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.
authors.affiliation: Tianjin Normal University, Institute of Bioinformatics and Drug Discovery, China. lifescience@san.rr.com
authors.forename: Qi-Shi
authors.initials: QS
authors.lastname: Du
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Chou
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019295:Computational Biology; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D011480:Protease Inhibitors; D014764:Viral Proteins; C000706207:3C-like protease, SARS coronavirus; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases