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TitleCoxsackievirus A10 atomic structure facilitating the discovery of a broad-spectrum inhibitor against human enteroviruses.
Journal, issue, pagesCell Discov, Vol. 5, Page 4, Year 2019
Publish dateJan 15, 2019
AuthorsJinhuan 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 AbstractCoxsackievirus 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.
External linksCell Discov / PubMed:30652025 / PubMed Central
MethodsEM (single particle)
Resolution2.84 - 3.12 Å
Structure data

9674

6iij

EMDB-9674, PDB-6iij:
Cryo-EM structure of CV-A10 mature virion
Method: EM (single particle) / Resolution: 2.84 Å

9675

6iio

EMDB-9675, PDB-6iio:
Cryo-EM structure of CV-A10 native empty particle
Method: EM (single particle) / Resolution: 3.12 Å

Chemicals

ChemComp-SPH:
SPHINGOSINE / Sphingosine

Source
  • coxsackievirus a10
KeywordsVIRAL PROTEIN / Coxsackievirus A10 / Mature virion

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