{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:51:25Z","timestamp":1791287485288,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T00:00:00Z","timestamp":1522108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institutes of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21 AI130807"],"award-info":[{"award-number":["R21 AI130807"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1132796"],"award-info":[{"award-number":["OPP1132796"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cryptosporidiosis causes life-threatening diarrhea in children under the age of 5 years and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to the need for new drugs, better knowledge of drug properties that drive\n                    <jats:italic>in vivo<\/jats:italic>\n                    efficacy is needed to facilitate drug development. We report the identification of a piperazine-based lead compound for\n                    <jats:named-content content-type=\"genus-species\">Cryptosporidium<\/jats:named-content>\n                    drug development, MMV665917, and a new pharmacodynamic method used for its characterization. The identification of MMV665917 from the Medicines for Malaria Venture Malaria Box was followed by dose-response studies,\n                    <jats:italic>in vitro<\/jats:italic>\n                    toxicity studies, and structure-activity relationship studies using commercial analogues. The potency of this compound against\n                    <jats:named-content content-type=\"genus-species\">Cryptosporidium parvum<\/jats:named-content>\n                    Iowa and field isolates was comparable to that against\n                    <jats:named-content content-type=\"genus-species\">Cryptosporidium hominis<\/jats:named-content>\n                    . Furthermore, unlike nitazoxanide, clofazimine, and paromomycin, MMV665917 appeared to be curative in a NOD SCID gamma mouse model of chronic cryptosporidiosis. MMV665917 was also efficacious in a gamma interferon knockout mouse model of acute cryptosporidiosis. To determine if efficacy in this mouse model of chronic infection might relate to whether compounds are parasiticidal or parasitistatic for\n                    <jats:named-content content-type=\"genus-species\">C. parvum<\/jats:named-content>\n                    , we developed a novel\n                    <jats:italic>in vitro<\/jats:italic>\n                    parasite persistence assay. This assay suggested that MMV665917 was parasiticidal, unlike nitazoxanide, clofazimine, and paromomycin. The assay also enabled determination of the concentration of the compound required to maximize the rate of parasite elimination. This time-kill assay can be used to prioritize early-stage\n                    <jats:named-content content-type=\"genus-species\">Cryptosporidium<\/jats:named-content>\n                    drug leads and may aid in planning\n                    <jats:italic>in vivo<\/jats:italic>\n                    efficacy experiments. Collectively, these results identify MMV665917 as a promising lead and establish a new method for characterizing potential anticryptosporidial agents.\n                  <\/jats:p>","DOI":"10.1128\/aac.01505-17","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T06:40:57Z","timestamp":1516171257000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["A Novel Piperazine-Based Drug Lead for Cryptosporidiosis from the Medicines for Malaria Venture Open-Access Malaria Box"],"prefix":"10.1128","volume":"62","author":[{"given":"R. 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