Evolutionary trajectories of Nipah virus: Evaluating the antiviral efficacy of Kabasura Kudineer Chooranam.

Nipah virus (NiV) is a highly contagious zoonotic pathogen causing severe encephalitis and respiratory illnesses in humans. With a high fatality rate and no FDA-approved treatments, NiV poses a significant public health threat. This study conducts a comprehensive Bayesian phylogenetic analysis of all publicly available NiV genomes since the first human case. Additionally, a protein-protein interaction (PPI) network analysis focusing on Pteropus species was performed to identify potential therapeutic targets. High-throughput virtual screening assessed the inhibitory potential of Kabasura Kudineer Chooranam phytocompounds against these targets. Molecular dynamic simulations (MDS) were conducted to evaluate the stability and dynamic characteristics of NiV proteins bound to specific inhibitors. Bayesian phylogenetic analysis of 280 NiV genomes revealed two distinct clades among Indian isolates, highlighting significant regional diversity. Notably, the latest strain, OM135495, along with other NiV variants in Kerala, underscores the virus's rapid genetic evolution since 2015. The PPI network identified NiV-F, NiV-G, and NiV-N as key therapeutic targets. Among the tested phyto compounds, Vasicinone and Piperine exhibited strong binding affinities (-4.51 to -5.96 kcal/mol) and enhanced stability during MDS, suggesting their potential as antiviral agents. These findings indicate that phyto compounds may serve as viable alternatives for NiV treatment, paving the way for novel drug development. However, further validation through laboratory and animal studies is essential. This study enhances our understanding of NiV evolution, informs public health strategies, and contributes to preparedness for future outbreaks.