Myricetin, as a potential new antiviral agent against Rana grylio ranavirus (RGRV)

Ranaviruses are extremely lethal viruses that pose a significant threat to aquaculture. Therefore, developing therapeutic strategies is essential for controlling these viruses. Utilizing herbal bioactive ingredients for the prevention and management of aquatic diseases shows great promise. In this study, we evaluated the antiviral activity of four flavonoids against a Ranavirus (RGRV). The results indicated that myricetin (MYR), luteolin (LUT), epigallocatechin gallate (EGCG), and rutin (RUT) exhibited anti-RGRV activity in vitro. Among these, MYR demonstrated the most potent antiviral activity, which was found to be dose-dependent. Subsequently, we discovered that MYR inhibited all stages of RGRV infection, particularly the early stage of viral replication, by down-regulating the expression of immediate-early genes and delayed-early genes. Furthermore, MYR enhanced host cell immunity and reduced inflammation by up-regulating the JAK-STAT signaling pathway and down-regulating the NF-κB signaling pathway. The in vivo challenge assay showed that MYR significantly reduced the mortality rate of the pig frog (Rana grylio) infected with RGRV. In summary, MYR demonstrated excellent anti-RGRV activity and held considerable promise for development in aquaculture. Our investigation provided the basis for promoting the development of anti-Ranaviruses agents.