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Babesiosis is caused by intraerythrocytic, apicomplexan parasites of the genus <jats:italic>Babesia.<\/jats:italic> In the United States, human babesiosis is caused by <jats:italic>Babesia microti<\/jats:italic> and <jats:italic>Babesia duncani.<\/jats:italic> Current treatment for babesiosis includes either the combination of atovaquone and azithromycin or the combination of clindamycin and quinine. However, the side effects of these agents and the resistance posed by these parasites call for alternative approaches for treating human babesiosis. Proteases play several roles in the context of parasitic lifestyle and regulate basic biological processes including cell death, cell progression, and cell migration. Using the SYBR Green\u20101 assay, we screened a protease inhibitor library that consisted of 160 compounds against <jats:italic>B.\u2009duncani<\/jats:italic> in\u00a0vitro and identified 13 preliminary hits. Dose response assays of hit compounds against <jats:italic>B.\u2009duncani<\/jats:italic> and <jats:italic>B.\u2009microti<\/jats:italic> under in\u00a0vitro conditions identified five effective inhibitors against parasite growth. Of these compounds, we chose ixazomib, a proteasome inhibitor as a potential drug for animal studies based on its lower IC<jats:sub>50<\/jats:sub> and a higher therapeutic index in comparison with other compounds. Our results suggest that <jats:italic>Babesia<\/jats:italic> proteasome may be an important drug target and that developing this class of drugs may be important to combat human babesiosis.<\/jats:p>","DOI":"10.1111\/jeu.13064","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T15:24:43Z","timestamp":1731943483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of protease inhibitors on the intraerythrocytic development of <i>Babesia microti<\/i> and <i>Babesia duncani<\/i>, the causative agents of human babesiosis"],"prefix":"10.1111","volume":"72","author":[{"given":"Temitope","family":"Aderanti","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Purdue University Fort Wayne  Fort Wayne Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Purdue University Fort Wayne  Fort Wayne Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-1737","authenticated-orcid":false,"given":"Jose","family":"Thekkiniath","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Purdue University Fort Wayne  Fort Wayne Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.AC118.005771"},{"key":"e_1_2_6_3_1","first-page":"1","article-title":"Summary of notifiable diseases \u2013 United States, 2011","volume":"60","author":"Adams D.A.","year":"2013","journal-title":"MMWR. 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