Structure-Based identification and triplicate molecular dynamics evaluation of phytochemical inhibitors targeting the nipah virus nucleocapsid protein

Nipah virus (NiV) is a highly pathogenic zoonotic virus associated with severe encephalitis and respiratory illness, with high mortality rates and no approved specific antiviral therapy. The nucleocapsid (N) protein plays a crucial role in viral genome encapsidation and replication, making it a promising therapeutic target. Identifying effective inhibitors against the NiV N protein is therefore of significant clinical importance. This study employed a structure-based virtual screening approach to identify potential inhibitors targeting the NiV N protein. A antiviral compound library was screened using molecular docking, drug-likeness, and ADME profiling. Two lead molecules 7-Deacetoxy-7-oxogedunin and 4-Methoxynorsecurinine were shortlisted based on estimated binding affinity and intermolecular non-covalent interactions. Triplicate molecular dynamics simulations assessed complex stability through RMSD, RMSF, Rg, and SASA analyses. Principal Component Analysis revealed ligand-induced conformational flexibility. MM/PBSA based binding free energy calculations demonstrated stronger binding for 7-Deacetoxy-7-oxogedunin (- 28.48 kcal/mol) compared to 4-Methoxynorsecurinine (- 15.19 kcal/mol). Among the screened compounds, 7-Deacetoxy-7-oxogedunin exhibited superior binding stability, emerging as the most promising inhibitor. These findings provide a robust computational framework and a rational basis for further experimental validation and antiviral drug development targeting the NiV N protein.

The online version contains supplementary material available at https://doi.org/10.1007/s13337-026-00975-9.