Structure of the HRV-C 3C-Rupintrivir Complex Provides New Insights for Inhibitor Design

查看全文 作　　者：Shuai [1,5]Yuan;Kaiyue [1,3]Fan;Zhonghao [2,4]Chen;Yao [1]Sun;Hai [2,4]Hou;Ling [1]Zhu

机构地区：[1]CAS Key Laboratory of Infection and Immunity,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;[2]Key Laboratory for Space Bioscience and Space Biotechnology,School of Life Sciences,Northwestern Polytechnical University,Xi’an 710072,China;[3]Beijing Forestry University,No.35 Tsinghua East Road,Haidian District,Beijing 100083,China;[4]Institute of Medical Research,Northwestern Polytechnical University,Xi’an 710072,China;[5]Department of Molecular Biophysics and Biochemistry,Yale University,New Haven,CT 06511,USA

出　　处：《Virologica Sinica》索引2020年第35卷第4期,共10页

基　　金：supported by the National Key Research and Development Program(2018YFA0900801);National Science Foundation of China(31800145);the State Key Laboratory of Veterinary Etiological Biology,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences and the seed Foundation of Innovation and Creation for Graduate Students in Northwestern Polytechnical University ZZ2019279;sponsored by the Youth Innovation Promotion Association at the Chinese Academy of Sciences。 摘　　要：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-C153C 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. 关键词：Human rhinoviruses(HRVs) 3C protease Three-dimensional structures INHIBITORS Rupintrivir(AG7088)

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Structure of the HRV-C 3C-Rupintrivir Complex Provides New Insights for Inhibitor Design

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