Coronavirus main proteinase (3CLpro) structure:: Basis for design of anti-SARS drugs

A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (M-pro, also called 3CL(pro)), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) M-pro and for an inhibitor complex of porcine coronavirus [ transmissible gastroenteritis virus ( TGEV)] Mpro, and we constructed a homology model for SARS coronavirus (SARS-CoV) M-pro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV M-pro-mediated cleavage of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus 3C(pro) inhibitors may be modified to make them useful for treating SARS.