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.