Inhibitor-Protein Interactions in Japanese Encephalitis Virus: A Computational Approach to Antiviral Discovery

Abstract

Japanese Encephalitis Virus (JEV) is a mosquito-borne virus that poses a significant health threat, causing severe neurological complications. To explore potential therapeutic interventions, this study utilized computational techniques, including molecular docking and molecular dynamics simulations, to investigate the interaction of Withaferin A, a natural compound derived from Ashwagandha, with specific viral proteins (4HDH and 4K6M). The results indicate strong binding affinity and favorable interactions between Withaferin A and the target proteins, suggesting its potential to disrupt viral processes. The compound's adherence to Lipinski's Rule of Five and low toxicity profile further support its suitability for drug development. Additionally, Withaferin A exhibits immunomodulatory and cytotoxic properties, which could contribute to its antiviral activity. The study employed tools such as PyRx, Discovery Studio, Chimera, and GROMACS to conduct molecular docking and dynamics simulations, providing valuable insights into the potential mechanism of action of Withaferin A. While additional studies, including clinical validation, are necessary, these results position Withaferin A as a promising candidate for therapeutic intervention against JEV. This research contributes to the ongoing efforts to expand the arsenal of strategies to mitigate the impact of this menacing virus and protect vulnerable populations from its severe neurological effects.