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

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-03-06 DOI:10.1016/j.bmcl.2025.130162

Zhi-Zheng Wang , Chen-Xu Xiao , Wen-Li Huang , Yang Hu , Hui-Ting Zhang , Zhang Liu , Sheng-Hao Peng , Zigong Wei

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引用次数: 0

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.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.