Utilizing Chemical Genomics to Identify Cytochrome as a Novel Drug Target for Chagas Disease

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Chagas Disease, or American trypanosomiasis, is caused by the kinetoplastid protozoan Trypanosoma cruzi and is primarily transmitted to a mammalian host via a triatomine insect vector (the “kissing bug”) infected with T. cruzi parasites. Although discovered in 1909 by the physician Dr. Carlos Chagas, the disease gained recognition by the public health community only following a major outbreak in Brazil during the 1960s. Approximately eight million people (primarily in Central and South America) are infected with T. cruzi and cases are becoming more widespread due to migration out of the endemic regions. Current treatment options have severe problems with toxicity, limited efficacy, and long administration. Hence, discovery of new drugs for treatment of Chagas disease has become of prime interest to the biomedical research community. In this study, we report identification of a potent inhibitor of T. cruzi growth and use a chemical genetics-based approach to elucidate the associated mechanism of action. We found that this compound, GNF7686, targets cytochrome b, a component of the mitochondrial electron transport chain crucial for ATP generation. Our study provides new insights into the use of phenotypic screening to identify novel targets for kinetoplastid drug discovery.

Vyšlo v časopise: Utilizing Chemical Genomics to Identify Cytochrome as a Novel Drug Target for Chagas Disease. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005058
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005058

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