Identification of new Drugs Against Chagas Disease through Genomics and Bioinformatics Strategies

Abstract

Chagas disease, caused by the protozoan parasite Trypanosomacruzi, is a major cause of mortality and morbidity in tropical and subtropical regions. In the absence of an effective vaccine, its control is highly dependent on the treatment of infected patients. However, only two drugs, nifurtimox and benzinidazole, are officially used for treating Chagas disease. Also, these drugs are incapable of generating radical cure and display high toxicity. Under this perspective, this study aimed to identify new therapies against Chagas disease, making use of a bioinformatics approach. Thus, theT. cruzi genome database was initially employed for selecting potential therapeutic targets (proteins) involved in intracellular transport mechanisms. In the second phase, each of the selected therapeutic targets was used to interrogate two databases that are able to identify inhibitors (drugs) based on homology with proteins from other species for which effective drugs are already available. This process, called "drug repositioning", allowed the identification of ten (10) new compounds with the potential to eliminate or inhibit the growth of T. cruzi parasites. The identification of these drugs may open new perspectives for the treatment of Chagas disease.

Keywords: Chagas; Trypanosoma cruzi; Drugs; Genomics; Bioinformatics.