Exploring the binding mechanism of the main proteinase in SARS-associated coronavirus and its implication to anti-SARS drug design.
The main proteinase of SARS-associated coronavirus (SARS-CoV) plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development. The important thing is to understand its binding mechanism with possible ligands. In this study, we investigated possible noncanonical interactions, potential inhibitors, and binding pockets in the main proteinase of SARS-CoV based on its recently determined crystal structure. These findings provide a wide clue to searching for anti-SARS drug. Interestingly, we found that similar structure patterns exist in SARS-CoV main proteinase with Poliovirus 3c Proteinase, Rhinovirus 3c Protease, Nsp4 Proteinase From Equine Arteritis Virus, Hepatitis C Virus Ns3 Protease, Hepatitis A Virus 3c Protease, and Dengue Virus Ns3 Protease. It suggests that the available drugs in these viruses could be used to fight SARS disease.
Zhang
Xue Wu
XW
HKU-Pasteur Research Center, Bioinformatics, 8 Sassoon Road, Hong Kong, China. xwzhang@hkucc.hku.hk
Yap
Yee Leng
YL
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases; D015195:Drug Design; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
D000998:Antiviral Agents; D014764:Viral Proteins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases