Temporal Modulation of Type I Interferon and NF-κB Signaling by Baicalin Suppresses Infectious Bronchitis Virus Replication and Inflammatory Response.

BACKGROUND: Infectious bronchitis virus (IBV) poses a significant threat to poultry health, and exploring effective antiviral agents is of considerable importance. This study aimed to investigate the antiviral activity of baicalin against IBV and its underlying immunomodulatory mechanisms. METHODS: The antiviral effect of baicalin was evaluated in chicken embryo kidney cells using various treatment schedules. Viral replication was assessed through nucleocapsid protein expression and viral titers. Mechanistic studies involved analysis of key signaling pathways, IRF3 knockdown experiments, and proteasomal degradation assays. RESULTS: Baicalin (20 µg/mL) significantly inhibited IBV replication, with optimal efficacy observed when administered at 2 h post-infection. The compound demonstrated time-dependent regulation of antiviral and inflammatory pathways, enhancing the MDA5-MAVS-STAT1 axis and IFN-β signaling at late infection stage while showing biphasic modulation of NF-κB pathway. IRF3 was identified as essential for both anti-inflammatory and antiviral effects. Baicalin enhanced IκBα stability by inhibiting its proteasomal degradation. CONCLUSIONS: Baicalin suppresses IBV replication through coordinated enhancement of type I interferon response and temporal regulation of NF-κB pathway, with IRF3 serving as a key regulatory molecule. These findings provide mechanistic support for baicalin's potential as an anti-IBV therapeutic agent.