Research and Reports in Tropical Medicine (Jun 2023)
State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation
Abstract
Juan Carlos Gabaldón-Figueira,1 Nieves Martinez-Peinado,1 Elisa Escabia,1 Albert Ros-Lucas,1,2 Eric Chatelain,3 Ivan Scandale,3 Joaquim Gascon,1,2 María-Jesús Pinazo,2,3 Julio Alonso-Padilla1,2 1Barcelona Institute for Global Health (ISGlobal), Hospital Clínic—University of Barcelona, Barcelona, Spain; 2CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III (CIBERINFEC, ISCIII), Madrid, Spain; 3Drugs for Neglected Diseases Initiative (DNDi), Geneva, SwitzerlandCorrespondence: Julio Alonso-Padilla, Barcelona Institute for Global Health (ISGlobal), Hospital Clínic—University of Barcelona. Carrer Rosselló 149, Barcelona, 08036, Spain, Tel +34 932275400 – ext. 4284, Email [email protected]: Chagas disease is the most important protozoan infection in the Americas, and constitutes a significant public health concern throughout the world. Development of new medications against its etiologic agent, Trypanosoma cruzi, has been traditionally slow and difficult, lagging in comparison with diseases caused by other kinetoplastid parasites. Among the factors that explain this are the incompletely understood mechanisms of pathogenesis of T. cruzi infection and its complex set of interactions with the host in the chronic stage of the disease. These demand the performance of a variety of in vitro and in vivo assays as part of any drug development effort. In this review, we discuss recent breakthroughs in the understanding of the parasite’s life cycle and their implications in the search for new chemotherapeutics. For this, we present a framework to guide drug discovery efforts against Chagas disease, considering state-of-the-art preclinical models and recently developed tools for the identification and validation of molecular targets.Keywords: Chagas disease, Trypanosoma cruzi, drug development, screenings, target, animal models
