Coronavirus Main Proteinase (3CL~(pro)) Structure: Basis for Design of Anti-SARS Drugs

摘要

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)] M~(pro), 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 M~(pro) substrate. Molecular modeling suggests that available rhinovirus 3C~(pro) inhibitors may be modified to make them useful for treating SARS.