Approaches to advance drug discovery for neglected tropical diseases

Abstract

Neglected tropical diseases (NTDs), which include leishmaniasis, Chagas disease, human African trypanosomiasis (HAT), and schistosomiasis, remain public health problems in developing countries, as highlighted in the 2021-2030 WHO Roadmap on NTDs. This agenda sets the challenges for the control and elimination of NTDs by 2030. Fortunately, NTD drug discovery has shifted from traditional to modern strategies combining medicinal chemistry, phenotypic and molecular assays, multiparameter optimization, structural biology, and omics approaches. Structure- and ligand-based drug design have fostered NTD drug discovery by enabling data-driven molecular optimization, expansion to previously inaccessible chemical spaces, and knowledge building from biological data. These efforts have integrated parasite biology and medicinal chemistry to advance drug discovery in this key area of global health.