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Curr Med Chem. 2019 Jun 10. doi: 10.2174/0929867326666190610152934. [Epub ahead of print]

Repositioning of HIV Aspartyl Peptidase Inhibitors for Combating the Neglected Human Pathogen Trypanosoma cruzi.

Author information

1
Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro. Brazil.
2
Laboratório de Biologia Celular, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro. Brazil.
3
Laboratório de Estudos Integrados em Protozoologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro. Brazil.
4
Laboratório de Estudos Integrados em Bioquímica Microbiana Departamento de Microbiologia Geral Instituto de Microbiologia Paulo de Góes Universidade Federal do Rio de Janeiro - UFRJ Rio de Janeiro, Brazil RIO DE JANEIRO, Rio de Janeiro. Brazil.

Abstract

Chagas disease, caused by the flagellate parasite Trypanosoma cruzi, is a well-known neglected tropical disease. This parasitic illness affects 6-7 million people and can lead to severe myocarditis and/or complications of the digestive tract. The changes in its epidemiology facilitate co-infection with the human immunodeficiency virus (HIV), making even more difficult the diagnosis and prognosis. The parasitic infection is reactivated in T. cruzi/HIV co-infection, with the appearance of unusual manifestations in the chronic phase and the exacerbation of classical clinical signs. The therapeutic arsenal to treat Chagas disease, in all its clinical forms, is restricted basically to two drugs, benznidazole and nifurtimox. Both drugs are extremely toxic and the therapeutic efficacy is still unclear, making the clinical treatment a huge issue to be solved. Therefore, it seems obvious the necessity of new tangible approaches to combat this illness. In this sense, the repositioning of approved drugs appears as an interesting and viable strategy. The discovery of HIV aspartyl peptidase inhibitors (HIV-PIs) represented a milestone in the treatment of acquired immune deficiency syndrome (AIDS) and, concomitantly, a marked reduction in both the incidence and prevalence of important bacterial, fungal and parasitic co-infections was clearly observed. Taking all these findings into consideration, the present review summarizes the promising and beneficial data concerning the effects of HIV-PIs on all the evolutionary forms of T. cruzi and in important steps of the parasite's life cycle, which highlight their possible application as alternative drugs to treat Chagas disease.

KEYWORDS:

Chagas disease; Trypanosoma cruzi; HIV-PIs; drug repositioning; mode of action; physiological alterations.

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