Repurposing COVID-19 Compounds (via MMV COVID Box): Almitrine and Bortezomib Induce Programmed Cell Death in Trypanosoma cruzi

Chagas disease, caused by the protozoan <i>Trypanosoma cruzi</i>, affects millions globally, with limited treatment options available. Current therapies, such as benznidazole and nifurtimox, present challenges, including their toxicity, side effects, and inefficacy in the chronic phase. This study explores the potential of drug repurposing as a strategy to identify new treatments for <i>T. cruzi</i>, focusing on compounds from the Medicines for Malaria Venture (MMV) COVID Box. An initial screening of 160 compounds identified eight with trypanocidal activity, with almitrine and bortezomib showing the highest efficacy. Both compounds demonstrated significant activity against the epimastigote and amastigote stages of the parasite and showed no cytotoxicity in murine macrophage cells. Key features of programmed cell death (PCD), such as chromatin condensation, mitochondrial membrane potential disruption, and reactive oxygen species accumulation, were observed in <i>T. cruzi</i> treated with these compounds. The potential to induce controlled cell death of these two compounds in <i>T. cruzi</i> suggests they are promising candidates for further research. This study reinforces drug repurposing as a viable approach to discovering novel treatments for neglected tropical diseases like Chagas disease.