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  3. Discovery of Flavonol derivatives as porcine reproductive and respiratory syndrome virus inhibitors

Discovery of Flavonol derivatives as porcine reproductive and respiratory syndrome virus inhibitors

  • Bioorg Med Chem Lett. 2025 Jun 1:121:130162. doi: 10.1016/j.bmcl.2025.130162.
Zhi-Zheng Wang 1,  Chen-Xu Xiao 1,  Wen-Li Huang 1,  Yang Hu 1,  Hui-Ting Zhang 1,  Zhang Liu 1,  Sheng-Hao Peng 1,  Zigong Wei 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Biocatalysis and Enzyme Engineering, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, School of life sciences, Hubei University, Wuhan, Hubei, PR China.
  • 2 State Key Laboratory of Biocatalysis and Enzyme Engineering, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, School of life sciences, Hubei University, Wuhan, Hubei, PR China; Hubei Jiangxia Laboratory, Wuhan, Hubei, PR China. Electronic address: weizigong@163.com.
PMID: 40057134 DOI: 10.1016/j.bmcl.2025.130162
Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) causes serious threat to the global pig industry, and there was still no efficient treatment for porcine reproductive and respiratory syndrome (PRRS). Flavonol compounds were reported to show Antiviral activity against a series of different virus. In this study, we designed a series of flavonol derivatives as promising lead structure for PRRSV inhibitors. A flavonol derivative database with diverse structures was first generated, and their anti-PRRSV activity were test. Among these compounds, compound 4s showed promising anti-PRRSV activity with EC50 values of 0.45 μM. In addition, it exhibited low cytotoxicity with CC50 higher than 100 μM. We also found that compound 4s inhibited PRRSV might be by repressing the activity of nsp4 protease. Molecular modeling study revealed that compound 4s binding to nsp4 mainly relies on a salt bridge and hydrophobic interaction. Our results might provide a new way for the development of PRRSV inhibitors.

Keywords

Antiviral; Flavonol derivatives; PRRSV; nsp4.

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