Chagas’ disease is one of the most impactful and prevalent neglected tropical
diseases in the Americas, specially affecting the poor and underdeveloped areas in
Latin America. Aggravating this scenario, the medicines used in the current chemotherapy are old, toxic and present a low
efficacy to treat the chronic stage of this disease. In addition, resistant strains of Trypanosoma cruzi, the etiological agent,
are frequently reported. So, there is an imperative requirement for novel chemotherapeutic options to treat this debilitating
disease. In this context, peptidases have emerged as potential targets and, consequently, proteolytic inhibitors have confirmed
to be valuable drugs against several human pathologies. In this line of thinking, T. cruzi produces a major multifunctional
cysteine peptidase, named cruzipain, which directly and/or indirectly orchestrates several physiological and
pathological processes, which culminate in a successful parasitic infection. Taken together, these findings point out that
cruzipain is one of the most important targets for driving a chemotherapy approach against the human pathogen T. cruzi.
The present review summarizes some of the recent advances and failures in this area, with particular emphasis on recently
Keywords: Chagas’ disease, Trypanosoma cruzi, human pathogen, neglected tropical disease, cysteine peptidases, cruzipain,
proteolytic inhibitors, chemotherapy.
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