Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 117 | 2022

Repositioning drug strategy against Trypanosoma cruzi: lessons learned from HIV aspartyl peptidase inhibitors

Leandro Stefano Sangenito1,+, Claudia Masini d’Avila-Levy2, Marta Helena Branquinha1, André Luis Souza dos Santos1,3

1Universidade Federal do Rio de Janeiro, Instituto de Microbiologia Paulo de Góes, Departamento de Microbiologia Geral, Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Rio de Janeiro, RJ, Brasil
2Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Estudos Integrados em Protozoologia, Rio de Janeiro, RJ, Brasil
3Universidade Federal do Rio de Janeiro, Instituto de Química, Programa de Pós-Graduação em Bioquímica, Rio de Janeiro, RJ, Brasil

DOI: 10.1590/0074-02760210386
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Chagas disease (CD) is an old neglected problem that affects more than 6 million people through 21 endemic countries in Latin America. Despite being responsible for more than 12 thousand deaths per year, the disease disposes basically of two drugs for its treatment, the nitroimidazole benznidazole and the nitrofuran nifurtimox. However, these drugs have innumerous limitations that greatly reduce the chances of cure. In Brazil, for example, only benznidazole is available to treat CD patients. Therefore, some proof-of-concept phase II clinical trials focused on improving the current treatment with benznidazole, also comparing it with repositioned drugs or combining them. Indeed, repositioning already marketed drugs in view of combating neglected tropical diseases is a very interesting approach in the context of decreased time for approval, better treatment options and low cost for development and implementation. After the introduction of human immunodeficiency virus aspartyl peptidase inhibitors (HIV-PIs) in the treatment of acquired immune deficiency syndrome (AIDS), the prevalence and incidence of parasitic, fungal and bacterial co-infections suffered a marked reduction, making these HIV-PIs attractive for drug repositioning. In this line, the present perspective presents the promising and beneficial data concerning the effects of HIV-PIs on the clinically relevant forms of Trypanosoma cruzi (i.e., trypomastigotes and amastigotes) and also highlights the ultrastructural and physiological targets for the HIV-PIs on this parasite. Therefore, we raise the possibility that HIV-PIs could be considered as alternative treatment options in the struggle against CD.

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Financial support: FAPERJ, CNPq, CAPES (financial code 001).
+ Corresponding author:
Received 08 December 2021
Accepted 14 January 2022

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