Molecular Simulations Approach Identified New Potent Marburg Virus VP40 Inhibitors from African Natural Products

Abstract

Marburg virus, the causative agent of Marburg hemorrhagic fever, is a highly contagious and often fatal pathogen transmitted via bodily fluids, with the African fruit bat Rousettus aegyptiacus serving as its natural reservoir. The matrix protein mVP40 is essential for virion assembly and budding, making it a strategic target for antiviral drug development. In this study, we employed a computational screening pipeline to identify potential mVP40 inhibitors from a library of African natural compounds. Molecular docking, pharmacokinetic analysis, toxicity prediction, and molecular dynamics (MD) simulations were conducted to evaluate compound efficacy and stability. Twenty candidates showed higher binding affinities and favorable ADMET profiles compared to the reference drug, ribavirin. Among them, Sodwanone R, Chamuvaratin, and Epigallocatechin-3-gallate demonstrated superior binding stability and interaction profiles in MD simulations. These compounds exhibit strong inhibitory potential against mVP40 and warrant further experimental validation as promising antiviral agents against Marburg virus.