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-Structure paper
タイトル | Coxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses. |
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ジャーナル・号・ページ | Cell Discov, Vol. 5, Page 4, Year 2019 |
掲載日 | 2019年1月15日 |
著者 | Jinhuan Chen / Xiaohua Ye / Xue-Yang Zhang / Zhengdan Zhu / Xiang Zhang / Zhijian Xu / Zhanyu Ding / Gang Zou / Qingwei Liu / Liangliang Kong / Wen Jiang / Weiliang Zhu / Yao Cong / Zhong Huang / |
PubMed 要旨 | Coxsackievirus A10 (CV-A10) belongs to the 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 ...Coxsackievirus A10 (CV-A10) belongs to the 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 Å, 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. |
リンク | Cell Discov / PubMed:30652025 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.84 - 3.12 Å |
構造データ | |
化合物 | ChemComp-SPH: |
由来 |
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キーワード | VIRAL PROTEIN / Coxsackievirus A10 / Mature virion |