Baicalein activates the type I interferon signaling pathway to inhibit infectious bronchitis virus infection

ABSTACT Avian infectious bronchitis virus (IBV) is a γ-coronavirus that primarily affects young chicks and laying hens. Its extensive serotype diversity and high mutation rate limit the effectiveness of current vaccines, leading to substantial economic losses in the poultry industry. In this study, we demonstrated that baicalein exerts potent antiviral activity against IBV, with a half-maximal inhibitory concentration (IC 50 ) of 2.34 μM and a selectivity index (SI) of 17.39 in Vero cells. Baicalein inhibited multiple stages of the viral life cycle and reversed IBV-induced immunosuppression by activating the type I interferon (IFN-I) signaling pathway. Specifically, it upregulated the mRNA and protein expression of key components in the RLR signaling pathway, including the pattern recognition receptors MDA5 and RIG-I, as well as downstream molecules such as MAVS, TBK1, and IRF3. This upregulation promoted IRF3 phosphorylation and subsequent IFN-I production. Concurrently, baicalein activated the JAK/STAT1 signaling pathway, enhancing STAT1 phosphorylation and increasing the expression of interferon-stimulated genes (ISGs), including MX1 and OAS1, thereby synergistically reinforcing the antiviral state. In IBV-infected chicks, baicalein treatment significantly alleviated body weight loss and respiratory symptoms, reduced viral loads in the trachea and lung tissues, and upregulated the expression of key genes involved in both the RLR (MDA5, MAVS, IRF7, IFN-β) and JAK-STAT (STAT1, MX1 and OAS1) signaling pathways. In conclusion, baicalein demonstrates significant anti-IBV potential both in vitro and in vivo through dual regulation of the IFN-I signaling pathway, offering a promising perspective for the development of broad-spectrum anti-coronavirus therapeutics.