Abstract

Ethnopharmacological relevance The bulb of Lycoris radiata (L’Hér.) Herb. (Amaryllidaceae) has been widely utilized in Traditional Chinese Medicine (TCM) for its properties of “clearing heat and relieving toxicity” (Qing Re Jie Du) and “eliminating phlegm” (Qu Tan), and is frequently prescribed for throat inflammation, abscesses, and ulcers. Although lycorine is known as the main active alkaloid, its specific activity against the avian respiratory coronavirus, infectious bronchitis virus (IBV), remains unexplored, despite the plant's long-standing use for respiratory ailments. Aim of the study To investigate the antiviral efficacy and immunomodulatory mechanism of lycorine against IBV both in vitro and in vivo , and to provide pharmacological evidence supporting the traditional application of Lycoris radiata in treating infectious diseases. Materials and methods Antiviral efficacy was evaluated in DF-1 cells and a SPF chicken infection model by monitoring viral loads and pathology. Mechanisms were investigated via Western blot and qPCR targeting the MDA5 pathway, alongside molecular docking. Results Lycorine hydrochloride exhibited potent anti-IBV activity in vitro with a half-maximal effective concentration (EC 50 ) of 0.1055 ± 0.0139 μM and a high selectivity index (SI) of 534, indicating a superior safety profile. In vivo , oral administration significantly alleviated clinical symptoms, reduced viral shedding, and prevented severe IBV-induced tracheal and renal pathology in infected chickens. Mechanistic studies revealed that lycorine hydrochloride acts as an innate immune booster by activating the MDA5-mediated type I interferon (IFN-I) signaling pathway, thereby restoring host antiviral surveillance. Furthermore, molecular docking suggested a potential direct interaction between lycorine and the viral nsp2, indicating a possible dual mechanism of action. Conclusions By simultaneously restricting viral replication and boosting host immunity, lycorine