Exploring Natural Alkaloids as Potential Inhibitors of DENV2 Envelope Protein via Molecular Docking and Dynamics

ABSTRACT The Dengue virus (DENV) is a major mosquito‐borne viral disease that affects human life globally. Annually, 20000 deaths are reported worldwide, yet there is no FDA approved antiviral agent to treat DENV infection. The envelope (E) protein of DENV is involved in the initial attachment of the virus to the host cell membrane, making it a vital target for antiviral drug development. In this study, virtual screening of 100 natural alkaloids was done against DENV2 E‐protein using the molecular docking method. The top ten complexes were subjected to ADMET analysis and they showed acceptable pharmacokinetic behavior with no associated toxicity. Based on docking score, binding interactions, and pharmacokinetic characteristics, four systems were selected for density functional theory (DFT) study and molecular dynamics (MD) simulation, namely ergosin, quinine, camptothecin, and chelianthifoline. MD simulation analysis revealed that selected complexes remain stable during the course of 200 ns simulation time. Post‐simulation MM‐GBSA analysis further confirmed the stability of the ligands within the active site cavity of DENV2 E‐protein, as reflected by their higher negative binding free energies. These in silico results signify that identified natural alkaloids are promising candidates for DENV2 E‐protein inhibitors and may serve as a basis for future therapeutic investigations.