Unveiling the potential of Hamigeran-B from marine sponges as a probable inhibitor of Nipah virus RDRP through molecular modelling and dynamics simulation studies

The Nipah virus (NiV) is an emerging pathogenic paramyxovirus that causes severe viral infection with a high mortality rate. This study aimed to model the effectual binding of marine sponge-derived natural compounds (MSdNCs) towards RNA-directed RNA polymerase (RdRp) of NiV. Based on the functional relevance, RdRp of NiV was selected as the prospective molecular target and 3D-structure, not available in its native form, was modelled. The effectual binding of selected MSdNCs that fulfilled the pharmacokinetics properties were docked against RdRp and the binding energy (BE) of the interaction was compared with the BE of the interaction between standard antiviral compound Remdesivir and RdRp. The stability of the best-docked pose was further confirmed by molecular dynamics (MD) simulation and binding free energy calculations. The current study revealed that the hypothetical RdRp model showed ideal stereochemical features. Molecular docking, dynamic and energy calculations suggested that Hamigeran-B (1<i>R</i>,3<i>aR</i>,9<i>bR</i>)-7- bromo-6-hydroxy-3<i>a</i>,8-dimethyl-1-propan-2-yl-1,2,3,9<i>b</i>-tetrahydrocyclopenta[a]naphthalene-4,5-dione) is a potent binder (BE: -6.35 kcal/mol) to RdRp when compared with the BE of Remdesivir and RdRp (-4.98 kcal/mol). This study suggests that marine sponge-derived Hamigeran-B is a potential binder to NiV-RdRp and that the present in silico model provides insight for future drug discovery against NiV infections.