Discovery of small molecules against porcine reproductive and respiratory syndrome virus replication by targeting NendoU activity
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.
Authors
- Radha Charan Dash (ORCID: https://orcid.org/0000-0003-0696-4962)
- Brianna Issacs
- Mengqi Cheng (ORCID: https://orcid.org/0000-0003-3812-3463)
- M. Kyle Hadden (ORCID: https://orcid.org/0000-0001-9482-1712)
- Zhenming Liu (ORCID: https://orcid.org/0000-0002-8993-4015)
- Antonio E. Garmendia
- Yu-Ting Lai (ORCID: https://orcid.org/0000-0003-4530-9493)
- Young Tang (ORCID: https://orcid.org/0000-0001-6188-7758)
- Yue Su (ORCID: https://orcid.org/0000-0002-6987-3737)
- Jinlei Guo (ORCID: https://orcid.org/0000-0002-4594-9696)
- Shuangshuang Guo (ORCID: https://orcid.org/0000-0003-4852-5124)
- Jiaqi Zhu (ORCID: https://orcid.org/0000-0002-9066-5545)
- Andrew Wolek
- Qi Li (ORCID: https://orcid.org/0000-0002-8282-4884)
- Xin He (ORCID: https://orcid.org/0000-0003-1579-3536)
- Neha Mishra (ORCID: https://orcid.org/0000-0002-6776-2195)
- Xiuchun Tian (ORCID: https://orcid.org/0000-0002-8441-2154)
Institutions
- University of Connecticut (US)
- Peking University (CN)
- Institute for Systems Biology (US)
- Northwest A&F University (CN)
Publication Details
- Journal
- Journal of Virology
- Published
- 2024-12-31
- DOI
- https://doi.org/10.1128/jvi.02034-24
- Citations
- 1
- Primary Topic
- Animal Virus Infections Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.34
Funders
- U.S. Department of Agriculture
- National Institute of Food and Agriculture
- Chinese Universities Scientific Fund