Malays. J. Anal. Sci. Volume 30 Number 2 (2026): 1663

 

Research Article

 

Unveiling the inhibitory mechanisms of ribavirin, EGCG and ST-610 on NS3 helicase of DENV2 through docking and molecular dynamics simulations

 

Aina Hazimah Bahaman1, Bimo Ario Tejo1,2, Siti Munirah Mohd Faudzi1,3 and Mohd Basyaruddin Abdul Rahman1*

 

1 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

2 Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

3 Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

 

*Corresponding author: basya@upm.edu.my

 

Received: 1 September 2025; Revised: 12 January 2026; Accepted: 8 April 2026; Published: 28 April 2026

 

Abstract

Dengue virus (DENV) nonstructural protein 3 (NS3) helicase is essential for viral replication and therefore an ideal target for antiviral drug development. In this study, three compounds, epigallocatechin gallate (EGCG), ST-610 and ribavirin, were screened for inhibitory activity against DENV2 NS3 helicase using molecular docking and two independent 200 ns molecular dynamics (MD) simulations. Docking led to strong binding affinities, the highest of which was EGCG (–8.3 kcal/mol), then ST-610 (–7.8 kcal/mol) and ribavirin (–7.2 kcal/mol). MD simulations revealed structural stability in both runs throughout, with the lowest RMSD by EGCG (0.272 ± 0.019 nm) compared to ST-610 (0.345 ± 0.070 nm) and ribavirin (0.314 ± 0.031 nm). Residue flexibility analysis (RMSF) also highlighted EGCG as the most stabilizing ligand at the catalytic residues (0.130 ± 0.067 nm). Solvent accessible surface area (SASA) was highest in case of EGCG (22.20 ± 0.47 nm²) and represents good conformational flexibility, while ribavirin formed the highest number of hydrogen bonds (7.07 ± 1.17) but had lesser global stability. Together, these findings suggest that EGCG has stronger inhibitory activity through the coupling of high affinity binding and structural stabilization of catalytically important residues. The current work provides mechanistic insights into ligand-NS3 helicase interactions and recognizes EGCG as a candidate for designing dengue antiviral drugs.

 

Keywords: NS3 helicase, dengue virus, molecular docking, molecular dynamics simulation, antiviral drug design

 

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