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 3,4,5-trisphosphate (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.

To Cite This Article: Zhang W, Li S, Lu Y, Li C, Ding J, Lai C, Jiang H, Tang Y, Yang W and Ren W, 2026. Isorhamnetin inhibits feline infectious peritonitis virus replication by binding PI3K and suppressing the AKT/NF-κB pathways. Pak Vet J, 2026, 46(10): 2466-2477. http://dx.doi.org/10.29261/pakvetj/2026.234