# A Promising Anti-dengue Virus Carboxylated-Sesquiterpene Lactone from Stevia entreriensis (Asteraceae)

**Authors:** Jimena Borgo, Alejandro Rodríguez-Martínez, Mariel S. Wagner, Augusto E. Bivona, Claudia S. Sepúlveda, César A. N. Catalán, Horacio Pérez-Sánchez, Valeria P. Sülsen

PMC · DOI: 10.1021/acsomega.5c05127 · 2025-10-09

## TL;DR

A new compound from Stevia entreriensis shows strong anti-dengue virus activity with low toxicity, offering potential for drug development.

## Contribution

A novel carboxylated sesquiterpene lactone with potent anti-DENV activity and low cytotoxicity is identified and characterized.

## Key findings

- The compound has an EC50 of 2.36 μM and a selectivity index of 1070.6 against DENV serotype 2.
- Molecular modeling suggests interactions with DENV protease and polymerase targets.
- The compound shows low cytotoxicity (CC50 = 2527.7 μM).

## Abstract

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 Stevia
entreriensis (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 S. entreriensis 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.

## Full-text entities

- **Genes:** RAF1 (Raf-1 proto-oncogene, serine/threonine kinase) [NCBI Gene 5894] {aka CMD1NN, CRAF, NS5, Raf-1, c-Raf}
- **Diseases:** cytotoxicity (MESH:D064420)
- **Chemicals:** Carboxylated-Sesquiterpene Lactone (-)
- **Species:** Dengue virus (no rank) [taxon 12637]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12547525/full.md

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Source: https://tomesphere.com/paper/PMC12547525