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Online Journal of Bioinformatics©

Onl J Bioinform©


Established 1995

ISSN  1443-2250

 

Volume 27 (2) : 125-146, 2026.

RNA-dependent RNA polymerase inhibitors against Japanese encephalitis virus by virtual screening, MM/GBSA and molecular dynamics simulation.

 

Akshay Kumar Shukla1, Mohd Saeed2, Vivek Dhar Dwivedi3*, Ramesh Chandra Tripathi1*

 

1Department of Biological Sciences, Faculty of Science and Environment, Mahatma Gandhi Chitrakoot Gramodaya Vishwavidyalaya, Chitrakoot, Satna, India,2Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia.3Bioinformatics Research Division, Quanta Calculus, Greater Noida, India Correspondence: Vivek Dhar Dwivedi: vivek_bioinformatics@yahoo.com Ramesh Chandra Tripathi: rctbsmgcgv2@gmail.com

 

ABSTRACT

 

Shukla AK, Saeed M, Dwivedi VD, Tripathi RC., RNA-dependent RNA polymerase inhibitors against Japanese encephalitis virus by virtual screening, MM/GBSA and molecular dynamics simulation., Onl J Bioinform., 27 (2) : 125-146, 2026. Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is a major cause of viral encephalitis in Asia and the Western Pacific, causing considerable morbidity and mortality despite the availability of effective vaccines. The absence of approved antiviral therapies points to the urgent need to find new therapeutic agents that target critical viral proteins. In the present study, an integrated computational approach was employed to screen an Approved Drug Analog Compound Library against potential inhibitors for the RNA-dependent RNA polymerase (RdRp) domain of the JEV NS5 protein. A hierarchical virtual screening workflow was used to prioritize the top candidates, including high-throughput virtual screening (HTVS), Glide standard precision (SP) and extra precision (XP) docking, and MM/GBSA binding free energy calculations. The top 3 performing compounds were then subjected to 100 ns molecular dynamics simulations and trajectory-based MM/GBSA analyses to probe the stability of the protein-ligand complexes. Among the screened compounds, F6617-8473, F6617-8464, and F2173-1125 demonstrated superior docking scores and binding free energies compared with the reference inhibitor Galidesivir. These compounds interacted stably with key catalytic residues (Arg460, Arg474, Tyr610, Cys714, Arg742, Trp800, and Ile802) and also displayed good structural stability during the simulation, as indicated by the RMSD, RMSF, radius of gyration, solvent-accessible surface area, and protein-ligand interaction analysis. Trajectory MM/GBSA calculations further confirmed their high binding affinities, with F6617-8473 exhibiting the most favorable binding free energy. Together, these results highlight F6617-8473, F6617-8464, and F2173-1125 as promising lead compounds against JEV RdRp and lay a strong foundation for further experimental validation and the development of novel antiviral therapeutics against Japanese encephalitis virus.

 

Keywords:  Japanese encephalitis virus, RdRp, Drug discovery, Molecular simulation.

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