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.
Highlights
Introduction CoxsackievirusA10 (CV-A10) belongs to the enterovirus genus in the Picornaviridae family[1]
Overall structures of the Coxsackievirus A10 (CV-A10) mature virion and native empty particle (NEP) Cryo-EM images of purified CV-A10 samples revealed the presence of two types of particles, including filled particles representing the mature virion, and NEP (Supplementary Fig. S1a)
Our structures reveal that CV-A10 NEP is slightly expanded compared with the mature virion and displays opened two-fold axis channel and quasi-three-fold axis channel, comparable to those of EV-A7111,12
Summary
A10 (CV-A10) belongs to the enterovirus genus in the Picornaviridae family[1]. CVA10 infection has been linked to large epidemics of HFMD in different countries including Japan[2], France[3], and China[4,5]. Human enteroviruses can be categorized into four species, including A–D (http://www.picornaviridae.com/ enterovirus/enterovirus.htm). High-resolution structural information is available for a number of human enteroviruses, such as EV-A7111,12, CV-A1613,14, coxsackievirus B3
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