The main proteinase of SARS-associated coronavirus (SARS-CoV) plays an important role in viral transcription andreplication, and is an attractive target for anti-SARS drug development. The important thing is to understand its binding mechanismwith possible ligands. In this study, we investigated possible noncanonical interactions, potential inhibitors, and bindingpockets in the main proteinase of SARS-CoV based on its recently determined crystal structure. These findings provide a wide clueto searching for anti-SARS drug. Interestingly, we found that similar structure patterns exist in SARS-CoV main proteinase withPoliovirus 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 tofight SARS disease.