Progress in computational approach to drug development against SARS.
Since the outbreak of SARS (severe acute respiratory syndrome) in November 2002 in Southern China's 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 C(28)H(34)O(4)N(7)Cl, C(21)H(36(O)5)N(6) and C(21)H(36)O(5)N(6) (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.
Chou
Kuo-Chen
KC
Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130, USA. kchou@san.rr.com
Wei
Dong-Qing
DQ
Du
Qi-Shi
QS
Sirois
Suzanne
S
Zhong
Wei-Zhu
WZ
D003936:Diagnosis, Computer-Assisted; D015195:Drug Design; D006801:Humans; D008490:Medical Informatics; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use; D045169:Severe Acute Respiratory Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D010455:Peptides