Antiviral potential and chemical characterization of secondary metabolites from Strophanthus boivinii active against dengue and Zika viruses

Dengue virus (DENV) and Zika virus (ZIKV), two closely related orthoflaviviruses transmitted by Aedes mosquitoes, continue to pose major public health threats in tropical regions. [ 1 ] In Réunion Island, dengue epidemics have become recurrent, with 1,265 cases reported during the first half of 2024. Despite this burden, no effective antiviral treatment is currently available against ZIKV or DENV [ 2 ]. As part of a large-scale screening effort of 1,200 plant extracts from Malagasy endemic flora, we identified 10 extracts with significant antiviral activity. Among them, Strophanthus boivinii emerged as a promising candidate. We investigated its antiviral potential against ZIKV, using a molecular recombinant infectious clone expressing GFP (ZIKVGFP) [ 3 ], in human hepatoma (Huh7.5), alveolar epithelial (A549), and kidney epithelial (Vero E6) cell lines. The most active fraction (F19) showed IC 50 values of 0.01, 0.004, and 0.05 μg/mL, respectively, and CC 50 values>2, 0.25, and>100 μg/mL, corresponding to selectivity indices of>200, 62.5, and>2000, highlighting an excellent therapeutic window. Time-of-drug addition assays indicated that the active fraction acts during early stages of viral replication, likely interfering with viral translation or transcription processes. UPLC-HRMS 2 analysis coupled with molecular networking revealed the presence of cardenolide-type molecules in the active fraction. Ongoing work aims to isolate and identify the specific bioactive compounds responsible for the antiviral activity. Our findings highlight the potential of Strophanthus boivinii , a Malagasy endemic plant, as a source of antiviral lead compounds and reinforce the value of biodiversity hotspots for natural antiviral drug discovery. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany