{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:28:51Z","timestamp":1788899331119,"version":"build-2803163510"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Chagas' disease, caused by the parasite\n            <jats:italic>Trypanosoma cruzi<\/jats:italic>\n            , remains the leading cause of cardiopathy in Latin America with about 12 million people infected. Classic clinical manifestations derive from infection of muscle cells leading to progressive cardiomyopathy, while some patients develop megacolon or megaesophagus. A very aggressive clinical course including fulminant meningoencephalitis has been reported in patients who contract Chagas' disease in the background of immunodeficiency. This includes patients with human immunodeficiency virus infection as well as patients receiving immunosuppressive therapy for organ transplant. Currently, only two drugs are approved for the treatment of Chagas' disease, nifurtimox and benznidazole. Both have significant limitations due to common and serious side effects as well as limited availability. A promising group of new drug leads for Chagas' disease is cysteine protease inhibitors targeting cruzain, the major protease of\n            <jats:italic>T. cruzi<\/jats:italic>\n            . The inhibitor\n            <jats:italic>N<\/jats:italic>\n            -methyl-Pip-F-homoF-vinyl sulfonyl phenyl (\n            <jats:italic>N<\/jats:italic>\n            -methyl-Pip-F-hF-VS\u03c6) is in late-stage preclinical development. Therefore, the question arose as to whether protease inhibitors targeting cruzain would have efficacy in Chagas' disease occurring in the background of immunodeficiency. To address this question, we studied the course of infection in recombinase-deficient (Rag1\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) and normal mice infected with\n            <jats:italic>T. cruzi<\/jats:italic>\n            . Infections localized to heart and skeletal muscle in untreated normal animals, while untreated Rag1\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice showed severe infection in all organs and predominantly in liver and spleen. Treatment with the dipeptide\n            <jats:italic>N<\/jats:italic>\n            -methyl-Pip-F-hF-VS\u03c6 rescued immunodeficient animals from lethal Chagas' infection. The majority (60 to 100%) of inhibitor-treated Rag1\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice had increased survival, negative PCR, and normal tissues by histopathological examination.\n          <\/jats:p>","DOI":"10.1128\/aac.00436-07","type":"journal-article","created":{"date-parts":[[2007,8,14]],"date-time":"2007-08-14T00:41:45Z","timestamp":1187052105000},"page":"3932-3939","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":141,"title":["A Cysteine Protease Inhibitor Cures Chagas' Disease in an Immunodeficient-Mouse Model of Infection"],"prefix":"10.1128","volume":"51","author":[{"given":"Patricia S.","family":"Doyle","sequence":"first","affiliation":[{"name":"Tropical Diseases Research Unit and Sandler Center, Department of Pathology, University of California, San Francisco, San Francisco, California 94121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan M.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Tropical Diseases Research Unit and Sandler Center, Department of Pathology, University of California, San Francisco, San Francisco, California 94121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Engel","sequence":"additional","affiliation":[{"name":"Tropical Diseases Research Unit and Sandler Center, Department of Pathology, University of California, San Francisco, San Francisco, California 94121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"McKerrow","sequence":"additional","affiliation":[{"name":"Tropical Diseases Research Unit and Sandler Center, Department of Pathology, University of California, San Francisco, San Francisco, California 94121"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040014"},{"key":"e_1_3_2_3_2","first-page":"41","volume":"38","year":"2005","unstructured":"Altcheh, J., M. Biancardi, A. Lapena, G. Ballering, and H. Freilij. 2005. Congenital Chagas disease: experience in the Hospital de Ni\u00f1os, Ricardo Gutierrez, Buenos Aires, Argentina. Rev. Soc. Bras. Med. Trop.38:41-45.","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.10.5892-5902.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(90)90160-N"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/lt.20522"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1191\/0960327106het653oa"},{"key":"e_1_3_2_8_2","first-page":"210","volume":"51","year":"2001","unstructured":"CDC. 2001. Chagas' disease after organ transplantation\u2014United States. Morb. Mortal. Wkly. Rep.51:210-212.","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"e_1_3_2_9_2","first-page":"11","year":"1982","unstructured":"Chagas, C. 1982. Coletanea de trabalhos cientificos, 1909-1913, p. 11-79, 237-335. Editora Universidade de Brasilia, Brasilia, Brazil.","journal-title":"Coletanea de trabalhos cientificos"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1997.tb01077.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0037-86822006000100018"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)04128-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1984.tb02961.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm010459j"},{"key":"e_1_3_2_15_2","first-page":"550","volume":"29","year":"1982","unstructured":"Engel, J. C., J. A. Dvorak, E. L. Segura, and M. St. J. Crane. 1982. Trypanosoma cruzi: biological characterization of 19 clones derived from two chagasic patients. Growth kinetics in liquid medium. J. Protozool.29:550-560.","journal-title":"J. Protozool."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.111.5.597"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.4.725"},{"key":"e_1_3_2_18_2","first-page":"171","volume":"59","year":"1999","unstructured":"Engel, J. C., P. S. Doyle, and J. H. McKerrow. 1999. Trypanocidal effect of cysteine protease inhibitors in vitro and in vivo in experimental Chagas' disease. Medicina (Buenos Aires)59:171-175.","journal-title":"Medicina (Buenos Aires)"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1998.59.526"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02761999000700070"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02761999000700062"},{"key":"e_1_3_2_22_2","first-page":"135","volume":"57","year":"2000","unstructured":"Gallerano, R. R., and R. R. Sosa. 2000. Interventional study in the natural evolution of Chagas' disease. Evaluation of specific antiparasitic treatment. Retrospective-prospective study of antiparasitic therapy. Rev. Fac. Cien. Med. Univ. Nac. Cordoba57:135-162.","journal-title":"Rev. Fac. Cien. Med. Univ. Nac. Cordoba"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.9.5314-5320.2000"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/8.6.527"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762005000300020"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/4.2.105"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00017a002"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-002-0754-9"},{"key":"e_1_3_2_29_2","unstructured":"CDC response to infections related to human tissue transplantation. 2003"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(99)01398-8"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.2006.047357"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.t01-1-00596.x"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-10-200605160-00006"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2007.01311.x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1086\/314889"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00436-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00436-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T19:17:50Z","timestamp":1645471070000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00436-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11]]},"references-count":34,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2007,11]]}},"alternative-id":["10.1128\/AAC.00436-07"],"URL":"https:\/\/doi.org\/10.1128\/aac.00436-07","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11]]},"assertion":[{"value":"2007-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-08-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}