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Publication Abstract from PubMed

Human rhinoviruses (HRVs) are the predominant infectious agents for the common cold worldwide. The HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma. 3C protease, a highly conserved enzyme, cleaves the viral polyprotein during replication and assists the virus in escaping the host immune system. These key roles make 3C protease an important drug target. A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been determined. These structures shed light on the determinants of drug specificity. Here we describe the structures of HRV-C15 3C in free and inhibitor-bound forms. The volume-decreased S1' subsite and half-closed S2 subsite, which were thought to be unique features of enterovirus A 3C proteases, appear in the HRV-C 3C protease. Rupintrivir assumes an "intermediate" conformation in the complex, which might open up additional avenues for the design of potent antiviral inhibitors. Analysis of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.

Structure of the HRV-C 3C-Rupintrivir Complex Provides New Insights for Inhibitor Design.,Yuan S, Fan K, Chen Z, Sun Y, Hou H, Zhu L Virol Sin. 2020 Feb 26. pii: 10.1007/s12250-020-00196-4. doi:, 10.1007/s12250-020-00196-4. PMID:32103448^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.