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Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses

文献类型：期刊论文

作者Chen, Jinhuan1; Ye, Xiaohua2; Zhang, Xue-Yang2; Zhu, Zhengdan3; Zhang, Xiang1; Xu, Zhijian3; Ding, Zhanyu1,4; Zou, Gang2; Liu, Qingwei2; Kong, Liangliang1,4
刊名CELL DISCOVERY
出版日期2019-01-15
卷号5页码:15
ISSN号2056-5968
DOI10.1038/s41421-018-0073-7
通讯作者Cong, Yao(cong@sibcb.ac.cn) ; Huang, Zhong(huangzhong@ips.ac.cn)
英文摘要Coxsackievirus A10 (CV-A10) belongs to the Enterovirus species A and is a causative agent of hand, foot, and mouth disease. Here we present cryo-EM structures of CV-A10 mature virion and native empty particle (NEP) at 2.84 and 3.12 angstrom, respectively. Our CV-A10 mature virion structure reveals a density corresponding to a lipidic pocket factor of 18 carbon atoms in the hydrophobic pocket formed within viral protein 1. By structure-guided high-throughput drug screening and subsequent verification in cell-based infection-inhibition assays, we identified four compounds that inhibited CV-A10 infection in vitro. These compounds represent a new class of anti-enteroviral drug leads. Notably, one of the compounds, ICA135, also exerted broad-spectrum inhibitory effects on a number of representative viruses from all four species (A-D) of human enteroviruses. Our findings should facilitate the development of broadly effective drugs and vaccines for enterovirus infections.
WOS关键词NEUTRALIZING LINEAR EPITOPES ; 3-DIMENSIONAL STRUCTURE ; MONOCLONAL-ANTIBODIES ; CELLULAR RECEPTOR ; PICHIA-PASTORIS ; VIRAL CHALLENGE ; CAPSID BINDER ; VIRUS ; POLIOVIRUS ; PICORNAVIRUS
资助项目National Key R&D Program of China[2017YFA0503503] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB29040000] ; CAS Pilot Strategic Science and Technology Projects B[XDB08030201] ; National Natural Science Foundation of China[31670754] ; National Natural Science Foundation of China[31500153] ; National Natural Science Foundation of China[31670159] ; National Natural Science Foundation of China[31872747] ; National Natural Science Foundation of China[31872714] ; CAS-Shanghai Science Research Center[CAS-SSRC-YH-2015-01] ; CAS-Shanghai Science Research Center[DSS-WXJZ-2018-0002] ; CAS Major Science and Technology Infrastructure Open Research Projects ; K.C. Wong Education Foundation ; TOTAL Foundation
WOS研究方向Cell Biology
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000455654700001
源URL[http://119.78.100.183/handle/2S10ELR8/290707]  
专题中国科学院上海药物研究所
通讯作者Cong, Yao; Huang, Zhong
作者单位1.Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Mol Biol,CAS Ctr Excellence Mol Cel, Natl Ctr Prot Sci Shanghai,Shanghai Inst Biochem, Shanghai, Peoples R China
2.Univ Chinese Acad Sci, Chinese Acad Sci, Inst Pasteur Shanghai, CAS Key Lab Mol Virol & Immunol, Shanghai, Peoples R China
3.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res,Drug Discovery & Design, Shanghai, Peoples R China
4.Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai, Peoples R China
5.Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA
推荐引用方式
GB/T 7714		 Chen, Jinhuan,Ye, Xiaohua,Zhang, Xue-Yang,et al. Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses[J]. CELL DISCOVERY,2019,5:15.
APA Chen, Jinhuan.,Ye, Xiaohua.,Zhang, Xue-Yang.,Zhu, Zhengdan.,Zhang, Xiang.,...&Huang, Zhong.(2019).Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses.CELL DISCOVERY,5,15.
MLA Chen, Jinhuan,et al."Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses".CELL DISCOVERY 5(2019):15.

入库方式： OAI收割

来源：上海药物研究所

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