Repurposing of approved drugs towards Nipah virus treatment: an in silico docking, molecular dynamics simulation and a MM/GBSA approach

Abstract

The Nipah virus (NiV) is an emerging zoonotic pathogen that causes severe febrile encephalitis, transmitted from infected animals to humans. Since its initial outbreak in Malaysia, subsequent epidemics have occurred across Asia, including India, with mortality rates ranging from 40 to 75%. There are no approved vaccines, or antiviral treatments currently exist for NiV infections. In this study, molecular docking was conducted using 42 FDA-approved drugs targeting the Nipah virus glycoprotein-human receptor complex. Binding affinities and 2D interaction profiles were analyzed, revealing five promising candidates: Saquinavir, Nelfinavir, Simeprevir, Paritaprevir, and Tipranavir. These compounds exhibited strong binding affinities, ranging from - 9.8 to -11.1 kcal/mol. These five top potential drugs were subjected to molecular dynamics (MD) simulations for 200 ns to further assess their stability, flexibility and compactness. MM/GBSA analysis was employed to estimate their binding free energies. The MD simulations confirmed their favourable binding properties, demonstrating significant stability and minimal fluctuation during the stability. Subsequently, drug-likeness evaluations were performed to assess key pharmacokinetic parameters, including absorption, distribution, metabolism, excretion, and toxicity (ADMET), with an emphasis on toxicity prediction and drug-like properties. The results revealed stable interactions with minimal structural fluctuations, supporting their potential as repurposed therapeutics for Nipah virus infection. To evaluate their efficacy and contribute to the development of effective antiviral treatments against NiV, further in vivo testing in animal models and human trials is recommended.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00371-z.

Keywords: ADMET; Computer aided drug design (CADD); MM/GBSA; Molecular docking; Molecular dynamics simulation; Nipah virus; Virtual screening.