{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:40:18Z","timestamp":1772156418218,"version":"3.50.1"},"posted":{"date-parts":[[2024,8,12]]},"group-title":"Microbiology","reference-count":29,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T00:00:00Z","timestamp":1723420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Artemisinins are first-line treatment for malaria, prized for their extremely fast reduction of parasite load in patients. New fast-acting antimalarial compounds are urgently needed to counter artemisinin resistance, but the fast parasite reduction observed with artemisinins is rare among antimalarial compounds. Here we show that MMV1580853 has a very fast\n                  <jats:italic>in vitro<\/jats:italic>\n                  killing rate, comparable to that of dihydroartemisinin. Near-complete parasite growth inhibition was observed within 1 hour of treatment with MMV1580853 and dihydroartemisinin, while chloroquine, another fast-acting antimalarial, showed partial growth inhibition after 1h. MMV1580853 was reported to inhibit prenyltransferases, but its fast killing rate is inconsistent with this mechanism-of-action and we were unable to validate any of 3 annotated\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  prenyltransferases as MMV1580853 targets. MMV1580853 also did not phenocopy the inhibition phenotype of either chloroquine or dihydroartemisinin. These results indicate that MMV1580853 has a distinct mechanism-of-action leading to a very fast killing rate. MMV1580853 compound development and investigation of its mechanism-of-action will be critical avenues in the search for drugs matching the remarkable clinical efficacy of artemisinin.\n                <\/jats:p>","DOI":"10.1101\/2024.08.12.607553","type":"posted-content","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T12:45:16Z","timestamp":1723466716000},"source":"Crossref","is-referenced-by-count":1,"title":["A fast-acting inhibitor of blood-stage\n                  <i>P. falciparum<\/i>\n                  with mechanism distinct from artemisinin and chloroquine"],"prefix":"10.64898","author":[{"given":"Stephanie","family":"Kabeche","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Meister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3974-3816","authenticated-orcid":false,"given":"Ellen","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024081414550430000_2024.08.12.607553v1.1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-016-1675-x"},{"key":"2024081414550430000_2024.08.12.607553v1.2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01238-23"},{"key":"2024081414550430000_2024.08.12.607553v1.3","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.1c00527"},{"key":"2024081414550430000_2024.08.12.607553v1.4","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0962-2"},{"key":"2024081414550430000_2024.08.12.607553v1.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217452110"},{"key":"2024081414550430000_2024.08.12.607553v1.6","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12121"},{"key":"2024081414550430000_2024.08.12.607553v1.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219899110"},{"key":"2024081414550430000_2024.08.12.607553v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030949"},{"key":"2024081414550430000_2024.08.12.607553v1.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5433.1573"},{"key":"2024081414550430000_2024.08.12.607553v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.11.010"},{"key":"2024081414550430000_2024.08.12.607553v1.11","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29865"},{"key":"2024081414550430000_2024.08.12.607553v1.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.07026.x"},{"key":"2024081414550430000_2024.08.12.607553v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10727"},{"key":"2024081414550430000_2024.08.12.607553v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2021.127978"},{"key":"2024081414550430000_2024.08.12.607553v1.15","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-020518-115546"},{"key":"2024081414550430000_2024.08.12.607553v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.04.018"},{"key":"2024081414550430000_2024.08.12.607553v1.17","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.7.2370-2378.2004"},{"key":"2024081414550430000_2024.08.12.607553v1.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073530"},{"key":"2024081414550430000_2024.08.12.607553v1.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1806109115"},{"key":"2024081414550430000_2024.08.12.607553v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06221-1"},{"key":"2024081414550430000_2024.08.12.607553v1.21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66277"},{"key":"2024081414550430000_2024.08.12.607553v1.22","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9550-9_9"},{"key":"2024081414550430000_2024.08.12.607553v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11901"},{"key":"2024081414550430000_2024.08.12.607553v1.24","doi-asserted-by":"publisher","DOI":"10.1177\/1178636118808529"},{"key":"2024081414550430000_2024.08.12.607553v1.25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0250019"},{"key":"2024081414550430000_2024.08.12.607553v1.26","unstructured":"Pandemic Response Box supporting information. In: Medicines for Malaria Venture [Internet]. [cited 2 Aug 2024]. Available: https:\/\/www.mmv.org\/mmv-open\/pandemic-response-box\/pandemic-response-box-supporting-information"},{"key":"2024081414550430000_2024.08.12.607553v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20629-8"},{"key":"2024081414550430000_2024.08.12.607553v1.28","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193225"},{"key":"2024081414550430000_2024.08.12.607553v1.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414221111"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.08.12.607553","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:51:09Z","timestamp":1768459869000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.08.12.607553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,12]]},"references-count":29,"URL":"https:\/\/doi.org\/10.1101\/2024.08.12.607553","relation":{"has-review":[{"id-type":"doi","id":"10.1162\/2e3983f5.ea3b2352","asserted-by":"object"},{"id-type":"doi","id":"10.1162\/2e3983f5.3ca3bb92","asserted-by":"object"},{"id-type":"doi","id":"10.1162\/2e3983f5.fbdcad2c","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2024,8,12]]},"subtype":"preprint"}}