Tanomastat exerts multi-targeted inhibitory effects on viral capsid dissociation and RNA replication in human enteroviruses.

ABSTRACT:

Background

Global cyclical outbreaks of human enterovirus infections has positioned human enterovirus A71 (EV-A71) as a neurotropic virus of clinical importance. However, there remains a scarcity of internationally approved antivirals and vaccines.

Methods

In pursuit of repurposing drugs for combating human enteroviruses, we employed a comprehensive pharmacophore- and molecular docking-based virtual screen targeting EV-A71 capsid protein VP1-4, 3C protease, and 3D polymerase proteins. Among 15 shortlisted ligand candidates, we dissected the inhibitory mechanism of Tanomastat in cell-based studies and evaluated its in vivo efficacy in an EV-A71-infected murine model.

Findings

We demonstrated that Tanomastat exerts dose-dependent inhibition on EV-A71 replication, with c

SUBMITTER: Lim TYM 

PROVIDER: S-EPMC11419895 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature