Science · 2003 · 1.8K citations · 12 references
Life SciencesMedicinal ChemistryPharmacologyDrug DesignMolecular VirologyVirologyAntiviral PharmacologyProtein DesignProtein StructureProtein Structure ModelingViral StructureVirus StructureAntiviral Drug DesignAntiviral TherapeuticsHomologySevere Acute Respiratory SyndromeStructural VirologySubstrate Binding SitesViral Protease FunctionViral Therapeutic Targets
A novel coronavirus causes SARS, and its main proteinase (3CLpro) is a key therapeutic target. Crystal structures of human coronavirus 229E Mpro and a porcine coronavirus inhibitor complex were determined, and a homology model of SARS‑CoV Mpro was built. The structures reveal conserved substrate‑binding sites, confirmed by SARS‑CoV Mpro cleaving a TGEV substrate, indicating that rhinovirus 3Cpro inhibitors could be adapted to treat SARS.
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.
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A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome
Dean D. Erdman, Goldsmith Cs, Zaki et al. · New England Journal of Medicine · 2003 · 4.5K citations
Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome
Paul A. Rota, M. Steven Oberste, Stephan S. Monroe et al. · Science · 2003 · 2.6K citations · Full text