Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses | |
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 |
2019-01-15 | |
卷号 | 5页码:15 |
ISSN号 | 2056-5968 |
DOI | 10.1038/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. |
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关键词 | NEUTRALIZING LINEAR EPITOPES ; 3-DIMENSIONAL STRUCTURE ; MONOCLONAL-ANTIBODIES ; CELLULAR RECEPTOR ; PICHIA-PASTORIS ; VIRAL CHALLENGE ; CAPSID BINDER ; VIRUS ; POLIOVIRUS ; PICORNAVIRUS |
WOS研究方向 | Cell Biology |
语种 | 英语 |
出版者 | NATURE PUBLISHING GROUP |
WOS记录号 | WOS:000455654700001 |
内容类型 | 期刊论文 |
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. |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论