Cysteine Protease Inhibitors Cure an Experimental Trypanosoma cruzi Infection

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Cysteine Protease Inhibitors Cure an Experimental Trypanosoma cruzi Infection

Trypanosoma cruzi is the causative agent of Chagas' disease. The major protease, cruzain, is a target for the development of new chemotherapy. We report the first successful treatment of an animal model of Chagas' disease with inhibitors designed to inactivate cruzain. Treatment with fluoromethyl ketone-derivatized pseudopeptides rescued mice from lethal infection. The optimal pseudopeptide sca...

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Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi.

Cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi, is a target of rational drug design for chemotherapy of Chagas' disease. The precise biological role of cruzain in the parasite life cycle and the mechanism involved in the trypanocidal effect of cysteine protease inhibitors are still unclear. Here we report biological and ultrastructural alterations caused by cys...

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A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi.

Cruzain is an essential cysteine protease of Trypanosoma cruzi and a therapeutic target for Chagas' disease. Eight dogs were infected with T. cruzi; three were treated with an inhibitor of cruzain, K777, for 14 days. Treatment with K777 abrogated myocardial damage by T. cruzi, as documented by histopathological lesion scores and serum troponin I levels.

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To confirm that Beagle dogs are a good experimental model for Chagas disease, we evaluated hematological alterations during the acute and chronic phases in Beagle dogs infected with the Y, Berenice-78 (Be-78) and ABC strains of Trypanosomacruzi, correlating clinical signs with the parasitemia curve. We demonstrate that the acute phase of infection was marked by lethargy and loss of appetite. Si...

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ژورنال

عنوان ژورنال: Journal of Experimental Medicine

سال: 1998

ISSN: 0022-1007,1540-9538

DOI: 10.1084/jem.188.4.725