Yong-Qi Guo ,Meng-Hang Wang ,Ning Tang ,Yu-Bo Zhao ,Li-Jing Wo ,De-Xin Liang ,Rui Huang ,Yan-Dong Tang , Ying-Jie Sun , Xin Yin 

J Adv Res. 2025 May 10:S2090-1232(25)00309-1. doi: 10.1016/j.jare.2025.05.016. Online ahead of print.

Abstract

Introduction: Alpha-herpesvirus poses significant health risks to humans and challenges to animal husbandry. Currently, the clinically approved antiviral drug Acyclovir exhibits limitations, including drug resistance and adverse effects. The development of broad-spectrum antiviral agents against alpha-herpesvirus is urgently needed.

Objective: This study aimed to discover a novel antiviral drug with the capacity to broadly inhibit various alpha-herpesviruses.

Methods: In this study, we conducted a high-content screening of 1,500 chemical compounds to identify potential antiviral candidates. The antiviral mechanisms were explored using phenotypic experiments, untargeted metabolomics, and molecular docking.

Results: We discovered that Antimycin A effectively inhibits the replication of various alpha-herpesviruses, including herpes simplex virus 1 (HSV-1), bovine herpesvirus 1 (BHV-1), and pseudorabies virus (PRV). Our study revealed that Antimycin A inhibits viral replication by disrupting the formation of pyrimidinosomes that are essential for efficient viral infection. Finally, Antimycin A effectively inhibited viral infection, prevented tissue damage, and enhanced survival in PRV-infected BALB/c mice, confirming its in vivo efficacy.

Conclusion: Antimycin A emerges as a promising lead candidate for the development of antiviral therapies against alpha-herpesvirus infections.

Keywords: Alpha-herpesviruses; Antimycin A; DHODH; Pyrimidinosomes; VDAC3.