Drug discovery for leishmaniasis and chagas disease: compound design and therapeutic strategies

Neglected tropical diseases (NTDs) such as leishmaniasis and Chagas disease remain pressing global-health challenges. Caused by the protozoa Leishmania and Trypanosoma cruzi, these infections persist where poverty, poor access to care and vector exposure intersect, and their global impact is growing with migration and climate change (de Brito et al., 2024). Although therapeutic options have improved, limitations persist, such as long regimens, toxicity, variable efficacy, and the threat of resistance.

This Research Topic was designed to showcase strategies that could change therapeutic trajectories, moving beyond incrementalism. These approaches include rational compound design anchored in target biology and pharmacokinetics/pharmacodynamics (PK/PD), phenotypic discovery linked to early target deconvolution, host-directed and delivery innovations, and, where appropriate, resistance-aware combinations. Five articles were accepted; all focused on Leishmania biology and therapy. While no Chagas disease studies were included, several mechanistic and translational insights are likely applicable to T. cruzi, particularly where pathogen pathways or host responses are conserved.