{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:02:32Z","timestamp":1791219752735,"version":"4.1.0"},"reference-count":36,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,3]]},"abstract":"<jats:p>Single-dose therapies for malaria have been proposed as a way to reduce the cost and increase the effectiveness of antimalarial treatment. However, no compound to date has shown single-dose activity against both the blood-stage <jats:italic>Plasmodium<\/jats:italic> parasites that cause disease and the liver-stage parasites that initiate malaria infection. Here, we describe a subset of cytochrome <jats:italic>bc<\/jats:italic><jats:sub>1<\/jats:sub> (cyt <jats:italic>bc<\/jats:italic><jats:sub>1<\/jats:sub>) inhibitors, including the novel 4(1<jats:italic>H<\/jats:italic>)-quinolone ELQ-400, with single-dose activity against liver, blood, and transmission-stage parasites in mouse models of malaria. Although cyt <jats:italic>bc<\/jats:italic><jats:sub>1<\/jats:sub> inhibitors are generally classified as slow-onset antimalarials, we found that a single dose of ELQ-400 rapidly induced stasis in blood-stage parasites, which was associated with a rapid reduction in parasitemia in vivo. ELQ-400 also exhibited a low propensity for drug resistance and was active against atovaquone-resistant <jats:italic>P. falciparum<\/jats:italic> strains with point mutations in cyt <jats:italic>bc<\/jats:italic><jats:sub>1<\/jats:sub>. Ultimately, ELQ-400 shows that cyt <jats:italic>bc<\/jats:italic><jats:sub>1<\/jats:sub> inhibitors can function as single-dose, blood-stage antimalarials and is the first compound to provide combined treatment, prophylaxis, and transmission blocking activity for malaria after a single oral administration. This remarkable multi-stage efficacy suggests that metabolic therapies, including cyt <jats:italic>bc<\/jats:italic><jats:sub>1<\/jats:sub> inhibitors, may be valuable additions to the collection of single-dose antimalarials in current development.<\/jats:p>","DOI":"10.4269\/ajtmh.14-0553","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T02:21:46Z","timestamp":1430187706000},"page":"1195-1201","source":"Crossref","is-referenced-by-count":43,"title":["Inhibition of Cytochrome bc1 as a Strategy for Single-Dose, Multi-Stage Antimalarial Therapy"],"prefix":"10.4269","volume":"92","author":[{"given":"Allison M.","family":"Stickles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Min","family":"Ting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne M.","family":"Morrisey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Mather","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Meermeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April M.","family":"Pershing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac P.","family":"Forquer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen P.","family":"Miley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sovitj","family":"Pou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf W.","family":"Winter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Hinrichs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane X.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kami","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil B.","family":"Vaidya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Riscoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Nilsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"R1","series-title":"World Malaria Report 2013","author":"World Health Organization","year":"2013"},{"key":"R2","series-title":"Trop Med Int Health","first-page":"121","article-title":"How do patients use antimalarial drugs? 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