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Trypanosoma evansi is the most widespread animal trypanosome of African origin causing the trypanosomosis known as \u201cSurra\u201d or \u201cderrengadera\u201d. Gelatin zymography combined with peptidase class-specific inhibitors identified four CPs in T. evansi lysates with relative masses of 28, 31, 36 and 40 kDa (p28, p31, p36 and p40). The CPs present in the T. evansi lysate preferentially hydrolyzed the Z-Phe-Arg-AMC fluorogenic substrate over Z-Gly-Arg-AMC and Z-Ala-Arg-AMC, and the hydrolysis of Z-Phe-Arg-AMC was inhibited by the K11777 (also known as SLV213) vinyl sulfone inhibitor with an apparent IC50 of 3.06 nM. Active-site labeling using the 125I-LHVS-PhOH vinyl sulfone inhibitor confirmed the identity of p28, p31, p36 and p40 as cathepsin-like peptidases. Partial purification of the T. evansi p40, analysis of its N-terminal peptide sequence and cross-reactivity with an anti-T. brucei (Tbr)CATL antiserum revealed its orthology to the C1A CPs present in T. b. brucei, T. cruzi, T. dionisii and T. rangeli. Treatment of infected mice with the pan-cathepsin irreversible inhibitor, K11777 (10 mg\/day), for 14 (n = 5) or 17 (n = 3) consecutive days was trypanocidal and significantly increased mice survival. These results validate TevCATL as a potential therapeutic target for the treatment of animal trypanosomosis caused by T. evansi.<\/jats:p>","DOI":"10.3390\/pathogens15090954","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:02:24Z","timestamp":1788858144000},"page":"954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trypanosoma evansi: Molecular Characterization and Validation of a Cathepsin-L-like Peptidase as a Potential Therapeutic Target"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7556-372X","authenticated-orcid":false,"given":"Adolfo","family":"Bremo","sequence":"first","affiliation":[{"name":"Grupo de Bioqu\u00edmica e Inmunolog\u00eda de Hemopar\u00e1sitos, Departamento de Biolog\u00eda Celular, Universidad Sim\u00f3n Bol\u00edvar, Sartenejas 1080, Estado Miranda, Venezuela"},{"name":"Laboratorio de Bioqu\u00edmica, Programa de Ciencias Veterinarias, Universidad Nacional Experimental Francisco de Miranda, Coro 4101, Estado Falc\u00f3n, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9258-8037","authenticated-orcid":false,"given":"Yenis G.","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Grupo de Bioqu\u00edmica e Inmunolog\u00eda de Hemopar\u00e1sitos, Departamento de Biolog\u00eda Celular, Universidad Sim\u00f3n Bol\u00edvar, Sartenejas 1080, Estado Miranda, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5300-4123","authenticated-orcid":false,"given":"Lilia M.","family":"Turcios","sequence":"additional","affiliation":[{"name":"Grupo de Bioqu\u00edmica e Inmunolog\u00eda de Hemopar\u00e1sitos, Departamento de Biolog\u00eda Celular, Universidad Sim\u00f3n Bol\u00edvar, Sartenejas 1080, Estado Miranda, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor R.","family":"Caffrey","sequence":"additional","affiliation":[{"name":"Tropical Disease Research Unit, Department of Pathology, University of California San Francisco, VAMC, San Francisco, CA 94121, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Matthew","family":"Bogyo","sequence":"additional","affiliation":[{"name":"Pathology Department, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"James H.","family":"McKerrow","sequence":"additional","affiliation":[{"name":"Tropical Disease Research Unit, Department of Pathology, University of California San Francisco, VAMC, San Francisco, CA 94121, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4266-2988","authenticated-orcid":false,"given":"Marisa","family":"Gonzatti","sequence":"additional","affiliation":[{"name":"Grupo de Bioqu\u00edmica e Inmunolog\u00eda de Hemopar\u00e1sitos, Departamento de Biolog\u00eda Celular, Universidad Sim\u00f3n Bol\u00edvar, Sartenejas 1080, Estado Miranda, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","unstructured":"Hoare, C.A. 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