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

Abstract

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 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.

• Authors: 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
• Journal: Cell discovery (Cell Discov) Vol. 5 Pg. 4 ( 2019) ISSN: 2056-5968 [Print] England
• PMID: 30652025 (Publication Type: Journal Article)