{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:34:45Z","timestamp":1787567685622,"version":"build-2736575974"},"reference-count":57,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["22H0250906"],"award-info":[{"award-number":["22H0250906"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003993","name":"Ministry of Agriculture, Forestry and Fisheries","doi-asserted-by":"publisher","award":["JPJ008837"],"award-info":[{"award-number":["JPJ008837"]}],"id":[{"id":"10.13039\/501100003993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Babesiosis is a disease brought on by intraerythrocytic parasites of the genus\n                    <jats:italic>Babesia<\/jats:italic>\n                    . Current chemotherapies are accompanied by side effects and parasite relapse. Therefore, it is crucial to develop highly effective drugs against\n                    <jats:italic>Babesia<\/jats:italic>\n                    . Cipargamin (CIP) has shown inhibition against apicomplexan parasites, mainly\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    and\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    . This study evaluated the growth-inhibiting properties of CIP against\n                    <jats:italic>Babesia<\/jats:italic>\n                    spp. and investigated the mechanism of CIP on\n                    <jats:italic>B. gibsoni<\/jats:italic>\n                    . The half inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) values of CIP against the in vitro growth of\n                    <jats:italic>B. bovis<\/jats:italic>\n                    and\n                    <jats:italic>B. gibsoni<\/jats:italic>\n                    were 20.2 \u00b1 1.4 and 69.4 \u00b1 2.2 nM, respectively. CIP significantly inhibited the growth of\n                    <jats:italic>B. microti<\/jats:italic>\n                    and\n                    <jats:italic>B. rodhaini<\/jats:italic>\n                    in vivo. Resistance was conferred by L921V and L921I mutations in BgATP4, which reduced the sensitivity to CIP by 6.1- and 12.8-fold. The inhibitory potency of CIP against BgATP4-associated ATPase activity was moderately reduced in mutant strains, with a 1.3- and 2.4-fold decrease in BgATP4\n                    <jats:sup>L921V<\/jats:sup>\n                    and BgATP4\n                    <jats:sup>L921I<\/jats:sup>\n                    , respectively, compared to that of BgATP4\n                    <jats:sup>WT<\/jats:sup>\n                    . An in silico investigation revealed reductions in affinity for CIP binding to BgATP4\n                    <jats:sup>L921V<\/jats:sup>\n                    and BgATP4\n                    <jats:sup>L921I<\/jats:sup>\n                    compared to BgATP4\n                    <jats:sup>WT<\/jats:sup>\n                    . Resistant strains showed no significant cross-resistance to atovaquone or tafenoquine succinate (TQ), with less than a onefold change in IC\n                    <jats:sub>50<\/jats:sub>\n                    values. Combining CIP with TQ effectively eliminated\n                    <jats:italic>B. microti<\/jats:italic>\n                    infection in SCID mice with no relapse, and parasite DNA was not detected by qPCR within 90 days post-infection. Our findings reveal the efficacy of CIP as an antibabesial agent, its limitations as a monotherapy due to resistance development, and the potential of combination therapy with TQ to overcome said resistance and achieve complete parasite clearance.\n                  <\/jats:p>","DOI":"10.7554\/elife.101128","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T11:28:17Z","timestamp":1726054097000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.101128","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and mechanism of action of cipargamin as an antibabesial drug candidate"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6361-8955","authenticated-orcid":true,"given":"Hang","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02t9fsj94","id-type":"ROR","asserted-by":"publisher"}],"name":"National Research Center for Protozoan Diseases, Obihiro University of Agriculture 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