Myricetin inhibits porcine circovirus 3 infection by targeting the viral capsid and modulating inflammatory and apoptotic pathways.

Porcine circovirus 3 (PCV3) is a prevalent swine pathogen that causes multiple clinical disorders and threatens the global pig industry. This study explored the anti-PCV3 activity and underlying mechanisms of myricetin, a natural flavonoid, in porcine kidney 15 (PK-15) cells. Results showed that myricetin suppressed PCV3 replication in a dose- and time-dependent manner, primarily by interfering with viral attachment and early entry. Molecular docking indicated myricetin binding to the PCV3 capsid. Further Western blotting validation revealed that myricetin also activated the Akt and ERK cascades, remodeled JAK-STAT signaling, and relieved PCV3-induced excessive autophagy and mitochondrial apoptosis. Network pharmacology screened six core host targets involved in the cell cycle, inflammation, autophagy, and apoptosis. Collectively, myricetin exhibited anti-PCV3 activity by targeting the viral capsid and regulating multiple host signaling pathways. This work provides experimental evidence for the development of myricetin as a promising natural agent against PCV3 infection.