Phenotypic screening approaches for Chagas disease drug discovery

Introduction: Chagas disease, caused by the parasite Trypanosoma cruzi, is a global public health issue. Current treatments targeting the parasite are limited to two old nitroheterocyclic drugs with serious side effects. The need for new and safer drugs has prompted numerous drug discovery efforts to identify compounds suitable for parasitological cure in the last decade. Areas covered: Target-based drug discovery has been limited by the small number of well-validated targets - the latest example being the failure of azoles, T. cruzi CYP51 inhibitors, in proof-of-concept clinical trials; instead phenotypic-based drug discovery has become the main pillar of Chagas R&D. Rather than focusing on the technical features of these screening assays, the authors describe the different assays developed and available in the field, and provide a critical view on their values and limitations in the screening cascade for Chagas drug development. Expert opinion: The application of technological advances to the field of Chagas disease has led to a variety of phenotypic assays that have not only changed the disease discovery landscape but have also helped us to gain a better understanding of parasite/host interactions. Recent examples of target resolution from phenotypic hits will uncover new opportunities for drug discovery for Chagas disease.