Lycorine Inhibits Chandipura Virus Replication In Vitro

Area of Science:

• Virology
• Molecular Biology
• Pharmacology

Background:

• Chandipura virus (CHPV) causes severe pediatric encephalitis in India with high mortality.
• No effective antiviral treatments are currently approved for CHPV infections.

Purpose of the Study:

• To evaluate the antiviral efficacy of lycorine, a plant-derived alkaloid, against CHPV.
• To investigate the mechanism of action of lycorine against CHPV replication.

Main Methods:

• In vitro antiviral assays were performed across multiple cell lines.
• Time-of-addition assays determined the stage of viral replication affected by lycorine.
• Quantitative RT-PCR assessed viral RNA synthesis inhibition.
• Molecular docking studies identified lycorine binding sites on the CHPV L protein.

Main Results:

• Lycorine demonstrated significant in vitro antiviral activity, reducing viral load by over 2.5 log₁₀.
• Lycorine exhibited low cytotoxicity and favorable selectivity indices.
• Antiviral effects were observed during early infection stages, without impacting viral entry or egress.
• Lycorine significantly inhibited CHPV positive-strand RNA synthesis.
• Molecular docking identified two high-affinity binding sites for lycorine in the viral RNA-dependent RNA polymerase catalytic domain.

Conclusions:

• Lycorine is a potent antiviral agent against Chandipura virus.
• Lycorine likely inhibits CHPV replication by targeting the viral RNA-dependent RNA polymerase.
• Lycorine represents a promising therapeutic candidate for CHPV and potentially other neurotropic RNA viruses.