Revealing the Dengue Antiviral Activity of Baper Tea Polyherbal: In Silico and In Vitro Approaches for the NS۲B/NS۳ Protease Inhibitors

Dengue virus serotype ۴ (DENV-۴) remains a significant global health burden, and no specific antiviral therapy has been approved to date. The exploration of plant-derived compounds as potential antiviral agents targeting the NS۲B/NS۳ protease complex represents a promising but largely underexplored therapeutic strategy. This study aimed to evaluate the antiviral activity of Baper Tea polyherbal against DENV-۴ by targeting the NS۲B/NS۳ protease via in silico and in vitro approaches. The cytotoxicity and antiviral activity were evaluated via MTT and Viral ToxGlo assays in DENV-۴-infected Vero cells to determine the CC۵۰, EC۵۰, and selectivity index (SI). Ten bioactive compounds from the Baper Tea polyherbal infusion were subjected to molecular docking against the NS۲B/NS۳ protease (PDB: ۵YVU) via AutoDock Vina ۱.۲.۰, and the binding interactions were analyzed via Discovery Studio. Baper Tea polyherbal infusion exhibited potent antiviral activity against DENV-۴, with an EC۵۰ of ۷۷.۵۷ μg/mL, a CC۵۰ of ۷,۳۴۵ μg/mL, and a favorable selectivity index of ۹۴.۶۹. Molecular docking studies revealed tetraacetyl-D-xylonic acid as the most promising compound, demonstrating a binding affinity (ΔG = -۶.۷۵ kcal/mol; Ki ۱۱.۲۹ μM) approximately ۴۵۷-fold stronger than that of the native ligand through six hydrogen bonds with catalytic residues (LYS B:۲۰۱, ASN B:۴۱۶, ALA B:۱۹۷, GLY B:۱۹۸, GLY B:۱۹۶, and ARG B:۴۶۳). The secondary candidates included dihydroxanthin (ΔG -۶.۳۸ kcal/mol; Ki ۲۱.۲۳ μM) and ۲,۷-diphenyl-۱,۶- (ΔG -۶.۳۱ kcal/mol; Ki ۲۳.۷۴ μM). This study provides preliminary computational and in vitro evidence of the potential of Baper Tea polyherbal infusion constituents to inhibit NS۲B/NS۳ protease.

کلیدواژه ها:

dengue virus ، Antiviral ، protease inhibitors ، Drug discovery ، Phytotherapy