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

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.