Marine Natural Products as Potential Inhibitors Against Non-Structural Protein 5 of Dengue Virus Serotype 3: An In-Silico Investigation

Abstract

This study systematically evaluated marine natural products as potential inhibitors of the DENV-3 NS5 using an integrated structure-based computational approach. A comprehensive in-silico workflow incorporating molecular docking and MM-GBSA binding free-energy calculations was applied to assess ligand interactions with the MTase–RdRp inter-domain region of NS5. From a library of 49,367 marine-derived compounds, 377 candidates exhibited high binding affinity and strongly negative ΔG_bind values, indicating stable protein–ligand complex formation within the active site. In silico ADMET analysis suggested that six compounds, CMNPD21439, CMNPD273, CMNPD14420, CMNPD15549, CMNPD1425, and CMNPD2951, were identified as promising candidates, with favourable pharmacokinetic profiles with minimal predicted cardiotoxicity and central nervous system (CNS) toxicity.