In Vitro and In Silico Analyses Explore the Role of Flavonoid Classes in the Antiviral Activity of Plant Extracts Against the Dengue Virus

This study examined the relationship between flavonoid content and the antiviral effects of plant extracts against the dengue virus (DENV). Fourteen extracts from medicinal plants cultivated in Colombia, which were prepared by ultrasonic-assisted solvent extraction (UAE) and supercritical fluid extraction (SFE) were included. UHPLC/ESI-Q-Orbitrap-MS analysis identified forty-six flavonoids. Antiviral effect on viral adsorption was evaluated using the DENV-CPE-based assay. UAE extracts of <i>Scutellaria coccinea</i>, <i>Scutellaria incarnata</i>, and <i>Lippia alba</i> contained higher amounts of flavonoid glycosides (from 97.0% to 87.9%) than aglycones, and showed antiviral effect (IC₅₀: 3.0 to 65 µg/mL; SI: 0.4 to 71). In contrast, UAE and SFE extracts from <i>Lippia origanoides</i> had higher content of flavonoid aglycones (41.7% to 93.4%) than glycosides (0.0 to 58.3%) and showed no antiviral effect. Cluster and one-way ANOVA analyses revealed a positive correlation between increased levels of flavone glycosides in the extract and a strong antiviral effect. Docking analyses (AutoDock Vina) revealed that the flavonoid glycosides exhibited a higher binding affinity for the target proteins (E, Gas6-Axl, clathrin, and dynamin) than the aglycones did. This study establishes a scientific basis for using extracts rich in flavonoid glycosides, particularly flavones, as starting points for developing plant-based therapies to treat dengue.