Repurposing HIV protease inhibitors against west nile virus: insights from molecular docking and molecular dynamics simulations

Abstract

West Nile virus (WNV) is a neurotropic flavivirus lacking approved antiviral therapies. Here, we evaluated the repurposing potential of ten HIV protease inhibitors as inhibitors of the WNV NS2B–NS3 protease using molecular docking followed by molecular dynamics simulations. Structural, energetic, and interaction analyses revealed substantial differences in binding stability under dynamic conditions. Indinavir and Atazanavir consistently showed strong and stable interactions, low structural and positional fluctuations, persistent hydrogen bonding, and favorable binding free energies. In contrast, several inhibitors displayed transient binding despite favorable docking scores. These findings emphasize the importance of molecular dynamics in drug repurposing studies and identify Indinavir and Atazanavir as promising candidates for further experimental evaluation against WNV.