Isorhamnetin Inhibits Feline Infectious Peritonitis Virus Replication by Binding PI3K and Suppressing the AKT/NF-κB Pathways

This study investigated the anti-Feline infectious peritonitis virus (FIPV) effects of Isorhamnetin (ISO) and its mechanisms via modulation of the serine-threonine kinase/nuclear factor kappa-B (AKT/NF-κB) signalling pathways.These effects of ISO were evaluated by measuring viral levels, the protein expression levels of key components in the AKT/NF-κB pathways, and the production of inflammatory cytokines in-vitro.For the first time, we demonstrated that ISO directly targets and binds to phosphatidylinositol 3-kinase (PI3K), inhibiting its lipid kinase activity, reducing the generation of the second messenger phosphatidylinositol 3,4,5trisphosphate (PIP3), and consequently effectively blocking the phosphorylation and activation of downstream key proteins in the AKT and NF-κB pathways.This action ultimately led to the suppression of viral replication and the downregulation of key pro-inflammatory cytokines, such as interleukin-8 (IL-8).In conclusion, our findings indicate that ISO exerts anti-FIPV effects by targeting PI3K and inhibiting the AKT/NF-κB pathways, providing a mechanistic basis for further evaluation of its antiviral activity and warranting validation in feline in-vivo models.