Ethnopharmacology- and Chemotaxonomy-Guided Evaluation of <i>Apuleia leiocarpa</i> Bark and Leaf Extracts against Oropouche, Mayaro, Chikungunya, and Zika Viruses

<i>Apuleia leiocarpa</i> (Vogel) J.F. Macbr. (Fabaceae) is traditionally used to treat fever and inflammatory symptoms, supporting an ethnopharmacological rationale for antiviral investigation. In addition, the chemotaxonomic context of the genus <i>Apuleia</i>, characterized by the prevalence of flavonoids and triterpenoids typical of Fabaceae, provides a complementary framework for the selection of this species. Guided by ethnopharmacological use and chemotaxonomic evidence, this study evaluated the <i>in vitro</i> antiviral activity of ethanolic and aqueous extracts obtained from the leaves and stem bark of <i>A. leiocarpa</i> against Mayaro, Chikungunya, Zika, and Oropouche viruses. Chemical characterization of the extracts was performed using liquid chromatography-tandem mass spectrometry combined with computational metabolomics tools, including molecular networking and mass spectral database searches. Flavonoids, triterpenoids, and phenolic acids were putatively annotated in the extracts, and their presence was interpreted in the context of antiviral activities previously reported for these chemical classes, providing a qualitative framework for the observed antiviral responses. All extracts exhibited antiviral activity against at least one of the viruses tested. Notably, the ethanolic stem bark extract showed potent activity against Oropouche virus, with an EC₅₀ value of 14.85 μg/mL and a selectivity index of 51.50. These results indicate that the ethanolic bark extract of <i>A. leiocarpa</i> represents a promising and renewable source of natural antiviral leads.