Metal-based drug development for Neglected Diseases: new insights

Neglected Tropical Diseases affect more than 1 billion people across 149 countries, primarily in impoverished regions. Climate change is expanding mosquito habitats, increasing the transmission of arboviral diseases such as Dengue, Zika, and Chikungunya. In this work, we obtained POMs from three structural classes: decavanadates, lacunary Keggin species, and Hervé-type compounds with a vanadium core. They were evaluated against recombinant NS3-NS2B protease from Zika and Dengue. The assays revealed strong inhibition by POMs, whereas the monomeric species showed negligible inhibitory activity, suggesting that the large size and high negative charge of the oxoclusters may play a key role in the observed inhibitory effect. Compounds´ stability under the assay conditions was assessed by ⁵¹V NMR and visible spectroscopy, revealing that POMs remained largely stable under the buffer conditions employed. The most promising compounds were selected for in vitro antiviral assays against DENV-2, and their cytotoxicity was evaluated in Vero cells.