Discovery of Small Molecules Against Porcine Reproductive and Respiratory Syndrome Virus Replication by Targeting NendoU Activity

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2025 Jan 2

PMID 39745451

Authors

Jiaqi Zhu

Yunqiang Lai

Mengqi Cheng

Radha Charan Dash

Shuangshuang Guo

Jintong Guo

Yue Su

Andrew Wolek

Brianna Issacs

Zhenming Liu

Qi Li

Neha Mishra

Antonio Garmendia

M Kyle Hadden

X Cindy Tian

Xin He

Young Tang

Affiliations

Soon will be listed here.

Abstract

Importance: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the pig industry, and vaccination is the principal method to prevent this viral infection currently. However, vaccination often fails to provide protection against heterologous strains, highlighting the need for alternative strategies for broad protection. The nidoviral uridylate-specific endoribonuclease (NendoU) domain plays a crucial role in viral replication and evasion of host immune responses. In this study, we identified a group of new compounds with similar chemical structures that could interfere with NendoU enzyme activity. Among these compounds, A8-A2 significantly inhibited PRRSV replication in host cells with minimal cytotoxicity. Our findings provide a new direction for developing potent antiviral compounds that can offer broad protection against different PRRSV strains, thereby mitigating their impact on pig health and benefiting the husbandry industry.

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