Computational identification of multi-targeted bioactive phytocompounds as candidate drug molecules against Nipah virus infection

Nipah Virus (NiV) is a highly virulent zoonotic virus that leads to severe encephalitis and respiratory diseases with mortality rates estimated at 40–75%, sometimes up to 100% in specific outbreaks. NiV has outbreaks in South and Southeast Asia, particularly in Bangladesh, India, Philippines, Malaysia, Singapore, and so on. The WHO classifies NiV as a priority pathogen due to its high fatality rate, lack of approved antiviral drugs or vaccines, and pandemic potential spread by human-to-human transmission. Therefore, identifying novel therapeutic agents against NiV remains a critical global health priority now. Natural phytochemicals have gained increasing attention due to their diverse biological activities and, favorable safety profiles. In this study, we investigated 2271 unique phytocompounds as drug candidates induced from 261 medicinal plants having high antiviral activities through molecular docking interaction with the NiV G glycoprotein, F fusion protein, and L protein. Phytocompounds with significant binding affinity (< − 7.0 kcal/mol) were further assessed by, drug-likeness screening, ADME/T Profiling, network pharmacology, protein–ligand interaction analysis, density functional theory (DFT) calculations, and 100 ns MD simulation to investigate structural stability and interaction behavior. Docking results revealed strong binding affinity of several phytochemicals toward NiV proteins. Among which Absinthin, Cycloepiatalantin, and Diosgenin showed the most favorable interactions results. ADME/T analysis suggested high absorption, low predicted toxicity, and effective blood–brain barrier penetration. DFT analysis indicated a favorable electronic interaction potential of the phytochemicals. MD simulations suggested stable protein–ligand complexes supported by the following analysis, RMSD, RMSF, SASA, RoG, MM-PBSA, DCCM, and PCA. Overall, these findings suggest that these Phytocompounds may serve as potential candidates for further experimental validation as antiviral agents against NiV. Using large-scale Phytocompounds screening, this study identified candidate compounds with predicted bioactivity capable of interacting with NiV proteins, while helping to reduce the cost, time, and labor associated with conventional wet-laboratory experiments.