Lycorine Inhibits Chandipura Virus Replication In Vitro

Chandipura virus (CHPV), a neurotropic member of the Rhabdoviridae family, causes severe paediatric encephalitis outbreaks in India with high fatality rates and no approved antiviral therapies. In this study, lycorine, a plant‐derived alkaloid with established broad‐spectrum antiviral activity, was evaluated for its efficacy against CHPV. In vitro treatment with lycorine resulted in a > 2.5 log₁₀ reduction in viral, with minimal cytotoxicity and favourable selectivity indices across multiple cell lines. Time‐of‐addition assays demonstrated that lycorine exerts its antiviral effect during early stages of infection, without affecting the viral entry or egress. Quantitative RT‐PCR revealed a significant inhibition of CHPV positive‐strand RNA synthesis, indicating disruption of early replication steps. To elucidate the mechanism of action, molecular docking studies were performed using a structural model of CHPV L protein, based on high‐homology alignment with Vesicular Stomatitis Virus (VSV) polymerase. Docking and free energy calculations identified two high‐affinity lycorine‐binding sites within the RdRp catalytic domain, stabilized by hydrogen bonding and aromatic interactions. These findings suggest that lycorine may inhibit CHPV replication by targeting the viral RNA‐dependent RNA polymerase. Overall, this study highlights lycorine as a promising antiviral candidate against CHPV and potentially other neurotropic RNA viruses.