A Promising Anti-dengue Virus Carboxylated-Sesquiterpene Lactone from <i>Stevia entreriensis</i> (Asteraceae)

In the ongoing search for effective antiviral agents against dengue virus (DENV), we have isolated a promising compound from a relatively unexplored natural source. This study describes the isolation, structural elucidation, and biological evaluation of a carboxylated sesquiterpene lactone, desacyl grazielia acid tiglate, from <i>Stevia entreriensis</i> (Asteraceae). Using an integrated approach that combines phytochemical and virological techniques, we reveal the potent anti-DENV activity of this compound, characterized by low cytotoxicity and high selectivity against DENV serotype 2 (EC₅₀ = 2.36 μM, CC₅₀ = 2527.7 μM, and SI = 1070.6). Furthermore, molecular modeling studies suggest a specific interaction mechanism with the viral NS2B/NS3 protease and NS5 polymerase, highlighting potential targets for viral inhibition. Our findings emphasize the antiviral potential of <i>S. entreriensis</i> paving the way for the development of nature-inspired therapeutics against DENV. The interdisciplinary approach reinforces the role of natural products in discovering new antiviral drugs and provides a promising candidate for further medicinal chemistry optimization.