Structural characterization of Trypanosoma cruzi nitroreductase for the development of new drugs against Chagas Disease

• Grant number: 24/23341-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Miguel de Menezes Vaidergorn
• Grantee: Beatriz Silveira Augusto
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi and classified by the World Health Organization (WHO) as a neglected tropical disease, poses a significant public health threat, particularly in Latin America. It can lead to permanent sequelae and even be fatal. Currently, available treatments are limited to benznidazole and nifurtimox, which, while effective in the acute phase, show reduced efficacy in the chronic phase of the disease. Both are prodrugs that require activation mediated by nitroreductases (NTR), enzymes that play crucial roles in the reduction of nitro compounds across various organisms. Despite their therapeutic relevance, the tertiary and quaternary structures of Trypanosoma cruzi nitroreductase (TcNTR) remain unresolved. Therefore, it is essential to determine the enzyme's crystal structure to facilitate the development of new drugs against Chagas disease. To this end, we propose structural studies of the enzyme in its native state and in the presence of substrates, aiming to deepen our understanding of its interactions at the active site, thereby contributing to the development of more effective therapeutic approaches.