Molecular docking, molecular dynamic simulation, and ADME analysis of Moringa oleifera phytochemicals targeting NS5 protein: towards the development of novel anti-dengue therapeutics.

OBJECTIVES

Dengue virus (DENV), a single-stranded RNA virus from the Flaviviridae family, causes viral hemorrhagic fever and poses a global health threat due to limited diagnostics, treatments, and vaccines. The conserved NS5 protein, crucial for DENV replication, is a promising antiviral target. Antibody-dependent enhancement (ADE) complicates immunity, as serotype-specific antibodies may worsen infection. Moringa oleifera, rich in antiviral phytochemicals, shows potential as a DENV inhibitor by targeting proteomic, transcriptomic, and metabolomic pathways.

METHODS

This study employed molecular docking with 3D PubChem structures of bioactive compounds of M. oleifera to evaluate the binding affinity with DENV-2 NS5 proteins (PDB ID: 6KR2) using AutoDock Vina, and binding modes were analyzed using Discovery Studio. Further drug-likeness, oral bioavailability, ADME, and toxicity profiles were analyzed using SwissADME, ADMETSaR, and ADMETlab 3.0 web server. Complexes were subjected to molecular dynamics simulation (MDS) analysis using Desmond Schrodinger v2019.

RESULTS

Among the screened compounds, rhamnopyranosyl vincosamide (-9.0 kcal/mol), luteoxanthin (-8.6 kcal/mol), and luteolin (-8.3 kcal/mol) exhibited the most stable interactions and were further analyzed through molecular dynamics (MD) simulations. The results revealed that these phytochemicals interact with NS5 active-site residues, demonstrating significant inhibitory potential.

CONCLUSIONS

The study suggests that M. oleifera phytochemicals hold promise as DENV-2 NS5 inhibitors with minimal toxicity and favorable pharmacokinetic properties. These findings provide a strong foundation for further clinical investigations, potentially contributing to developing novel anti-dengue therapeutics.