Marine Natural Products as Potential Inhibitors of NS2b/NS3-Protease of Dengue Virus: An In-Silico Approach

Abstract

This study explores marine natural products as potential inhibitors of the NS2b/NS3-protease from dengue virus type-4 (DENV-4). A comprehensive in-silico approach, including molecular docking and MMGBSA calculations, was employed to screen and evaluate marine-derived compounds for their binding affinity to the protease active centre. Two novel compounds, CMNPD28799 and CMNPD28841, were identified as promising inhibitors of NS2b/NS3-protease, demonstrating strong binding affinities and binding-free energies. In silico ADMET analysis suggested these compounds possess favourable pharmacokinetic profiles with decent gut and mammalian kidney cell permeability as well as minimal predicted cardiotoxicity and central nervous system (CNS) toxicity.