Identification of Promising Marburg Virus VP24 Inhibitors using Molecular Simulations

Abstract

A total of 10,925 natural compounds from four databases were screened for VP24 binding affinity using AutoDock Vina. The top-scoring candidates were further assessed for drug-likeness, pharmacokinetics, and toxicity using SwissADME and ProTox-II. The most promising compounds underwent exhaustive molecular docking, followed by molecular dynamics (MD) simulations to evaluate binding stability. Free energy calculations using the MM-PB(GB)SA method quantified binding affinity. Ligand–protein interactions were analyzed using Protein-Ligand Interaction Profiler (PLIP) to assess key binding features. Among the two lead candidates, only one exhibited stable binding and strong interactions with VP24 hotspot residues. This compound holds potential as an antiviral agent against Marburg virus and warrants further validation through in vitro and in vivo studies.