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Health","award":["i01 BX003312"],"award-info":[{"award-number":["i01 BX003312"]}]},{"name":"US National Institutes of Health","award":["14S-RCS001"],"award-info":[{"award-number":["14S-RCS001"]}]},{"name":"US National Institutes of Health","award":["R01AI100569"],"award-info":[{"award-number":["R01AI100569"]}]},{"name":"US National Institutes of Health","award":["R01AI141412"],"award-info":[{"award-number":["R01AI141412"]}]},{"name":"US National Institutes of Health","award":["PR181134"],"award-info":[{"award-number":["PR181134"]}]},{"name":"US National Institutes of Health","award":["BX004522"],"award-info":[{"award-number":["BX004522"]}]},{"name":"U.S. Department of Defense Peer Reviewed Medical Research Program","award":["ARS-USDA CRIS 2090-32000-040-000-D"],"award-info":[{"award-number":["ARS-USDA CRIS 2090-32000-040-000-D"]}]},{"name":"U.S. Department of Defense Peer Reviewed Medical Research Program","award":["i01 BX003312"],"award-info":[{"award-number":["i01 BX003312"]}]},{"name":"U.S. Department of Defense Peer Reviewed Medical Research Program","award":["14S-RCS001"],"award-info":[{"award-number":["14S-RCS001"]}]},{"name":"U.S. Department of Defense Peer Reviewed Medical Research Program","award":["R01AI100569"],"award-info":[{"award-number":["R01AI100569"]}]},{"name":"U.S. Department of Defense Peer Reviewed Medical Research Program","award":["R01AI141412"],"award-info":[{"award-number":["R01AI141412"]}]},{"name":"U.S. Department of Defense Peer Reviewed Medical Research Program","award":["PR181134"],"award-info":[{"award-number":["PR181134"]}]},{"name":"U.S. Department of Defense Peer Reviewed Medical Research Program","award":["BX004522"],"award-info":[{"award-number":["BX004522"]}]},{"name":"US Department of Veterans Affairs Biomedical Laboratory Research and Development","award":["ARS-USDA CRIS 2090-32000-040-000-D"],"award-info":[{"award-number":["ARS-USDA CRIS 2090-32000-040-000-D"]}]},{"name":"US Department of Veterans Affairs Biomedical Laboratory Research and Development","award":["i01 BX003312"],"award-info":[{"award-number":["i01 BX003312"]}]},{"name":"US Department of Veterans Affairs Biomedical Laboratory Research and Development","award":["14S-RCS001"],"award-info":[{"award-number":["14S-RCS001"]}]},{"name":"US Department of Veterans Affairs Biomedical Laboratory Research and Development","award":["R01AI100569"],"award-info":[{"award-number":["R01AI100569"]}]},{"name":"US Department of Veterans Affairs Biomedical Laboratory Research and Development","award":["R01AI141412"],"award-info":[{"award-number":["R01AI141412"]}]},{"name":"US Department of Veterans Affairs Biomedical Laboratory Research and Development","award":["PR181134"],"award-info":[{"award-number":["PR181134"]}]},{"name":"US Department of Veterans Affairs Biomedical Laboratory Research and Development","award":["BX004522"],"award-info":[{"award-number":["BX004522"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Bovine babesiosis is a vector-borne disease transmitted by ticks that causes important losses in livestock worldwide. Recent research performed on the drugs currently used to control bovine babesiosis reported several issues including drug resistance, toxicity impact, and residues in edible tissue, suggesting the need for developing novel effective therapies. The endochin-like quinolones ELQ-316 and buparvaquone (BPQ) act as cytochrome bc1 inhibitors and have been proven to be safe and efficacious against related apicomplexans, such as Plasmodium spp. and Babesia microti, without showing toxicity in mammals. The objectives of this study are investigating whether ELQ-316, BPQ, and their combination treatment could be effective against Babesia bovis in an in vitro culture model and comparing with imidocarb (ID), the routinely used drug. Methods: In vitro cultured parasites starting at 2% percentage of parasitemia (PPE) were treated with BPQ, ELQ-316, ID, and the combinations of BPQ + ELQ-316 and ID + ELQ-316 at drug concentrations that ranged from 25 to 1200 nM, during four consecutive days. The IC50% and IC99% were reported. Parasitemia levels were evaluated daily using microscopic examination. Data were compared using the non-parametrical Mann\u2013Whitney and Kruskall\u2013Wallis test. Results: All drugs tested, whether used alone or in combination, significantly decreased the survival (p &lt; 0.05) of B. bovis in in vitro cultures. The combination of BPQ + ELQ-316 had the lowest calculated inhibitory concentration 50% (IC50%) values, 31.21 nM (IC95%: 15.06\u201368.48); followed by BPQ, 77.06 nM (IC95%: 70.16\u201386.01); ID + ELQ316, 197 nM (IC95%:129.0\u2013311.2); ID, 635.1 nM (IC95%: 280.9\u20132119); and ELQ316, 654.9 nM (IC95%: 362.3\u20131411). Conclusions: The results reinforce the higher efficacy of BPQ at affecting B. bovis survival and the potential synergistic effects of its combination with ELQ-316, providing a promising treatment option against B. bovis.<\/jats:p>","DOI":"10.3390\/pharmaceutics16111402","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T06:55:37Z","timestamp":1730357737000},"page":"1402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb Against Babesia bovis In Vitro"],"prefix":"10.3390","volume":"16","author":[{"given":"Natalia M.","family":"Cardillo","sequence":"first","affiliation":[{"name":"Animal Disease Research Unit, United States Department of Agriculture-Animal Research Unit (USDA-ARS), 3003 ADBF, WSU, Pullman, WA 99163, USA"},{"name":"Estaci\u00f3n Experimental INTA Paran\u00e1, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Buenos Aires 2290, Argentina"},{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas F.","family":"Villarino","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Lacy","sequence":"additional","affiliation":[{"name":"Animal Disease Research Unit, United States Department of Agriculture-Animal Research Unit (USDA-ARS), 3003 ADBF, WSU, Pullman, WA 99163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-5279","authenticated-orcid":false,"given":"Michael K.","family":"Riscoe","sequence":"additional","affiliation":[{"name":"VA Portland Healthcare System, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA"},{"name":"Department of Microbiology and Molecular Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph Stone","family":"Doggett","sequence":"additional","affiliation":[{"name":"VA Portland Healthcare System, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA"},{"name":"School of Medicine, Division of Infectious Diseases, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2680-6091","authenticated-orcid":false,"given":"Massaro W.","family":"Ueti","sequence":"additional","affiliation":[{"name":"Animal Disease Research Unit, United States Department of Agriculture-Animal Research Unit (USDA-ARS), 3003 ADBF, WSU, Pullman, WA 99163, USA"},{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chungwon J.","family":"Chung","sequence":"additional","affiliation":[{"name":"Animal Disease Research Unit, United States Department of Agriculture-Animal Research Unit (USDA-ARS), 3003 ADBF, WSU, Pullman, WA 99163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-2931","authenticated-orcid":false,"given":"Carlos E.","family":"Suarez","sequence":"additional","affiliation":[{"name":"Animal Disease Research Unit, United States Department of Agriculture-Animal Research Unit (USDA-ARS), 3003 ADBF, WSU, Pullman, WA 99163, USA"},{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ristic, M., Ambroise-Thomas, P., and Kreier, J.P. 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