{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:46:53Z","timestamp":1784810813328,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009601","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000}}],"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Onchocerciasis (river blindness), caused by the filarial worm <jats:italic>Onchocerca volvulus<\/jats:italic>, is a neglected tropical disease mostly affecting sub-Saharan Africa and is responsible for &gt;1.3 million years lived with disability. Current control relies almost entirely on ivermectin, which suppresses symptoms caused by the first-stage larvae (microfilariae) but does not kill the long-lived adults. Here, we evaluated emodepside, a semi-synthetic cyclooctadepsipeptide registered for deworming applications in companion animals, for activity against adult filariae (<jats:italic>i<\/jats:italic>.<jats:italic>e<\/jats:italic>., as a macrofilaricide). We demonstrate the equivalence of emodepside activity on SLO-1 potassium channels in <jats:italic>Onchocerca volvulus<\/jats:italic> and <jats:italic>Onchocerca ochengi<\/jats:italic>, its sister species from cattle. Evaluation of emodepside in cattle as single or 7-day treatments at two doses (0.15 and 0.75 mg\/kg) revealed rapid activity against microfilariae, prolonged suppression of female worm fecundity, and macrofilaricidal effects by 18 months post treatment. The drug was well tolerated, causing only transiently increased blood glucose. Female adult worms were mostly paralyzed; however, some retained metabolic activity even in the multiple high-dose group. These data support ongoing clinical development of emodepside to treat river blindness.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009601","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T05:07:58Z","timestamp":1622696878000},"page":"e1009601","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3231-4250","authenticated-orcid":true,"given":"Germanus 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Townson","year":"2005","journal-title":"Am J Trop Med Hyg"},{"issue":"Pt 3","key":"ppat.1009601.ref031","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1017\/S0031182004006523","article-title":"Efficacy of two cyclooctadepsipeptides, PF1022A and emodepside, against anthelmintic-resistant nematodes in sheep and cattle","volume":"130","author":"G von Samson-Himmelstjerna","year":"2005","journal-title":"Parasitology"},{"key":"ppat.1009601.ref032","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ijpddr.2020.04.003","article-title":"Efficacy evaluation of anthelmintic products against an infection with the canine hookworm (Ancylostoma caninum) isolate Worthy 4.1F3P in dogs","volume":"13","author":"PD Jimenez Castro","year":"2020","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"ppat.1009601.ref033","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3389\/fnins.2019.00154","article-title":"Latrophilins and teneurins in invertebrates: no love for each other?","volume":"13","author":"T Schoneberg","year":"2019","journal-title":"Front Neurosci"},{"issue":"15","key":"ppat.1009601.ref034","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.cub.2004.07.056","article-title":"Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans","volume":"14","author":"J Willson","year":"2004","journal-title":"Curr Biol"},{"issue":"6","key":"ppat.1009601.ref035","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.ijpara.2006.10.013","article-title":"Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans","volume":"37","author":"K Bull","year":"2007","journal-title":"Int J Parasitol"},{"issue":"14","key":"ppat.1009601.ref036","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.ijpara.2007.05.006","article-title":"The calcium-activated potassium channel, SLO-1, is required for the action of the novel cyclo-octadepsipeptide anthelmintic, emodepside, in Caenorhabditis elegans","volume":"37","author":"M Guest","year":"2007","journal-title":"Int J Parasitol"},{"issue":"12","key":"ppat.1009601.ref037","doi-asserted-by":"crossref","first-page":"e3401","DOI":"10.1371\/journal.pntd.0003401","article-title":"Characterization of the Ca2+-gated and voltage-dependent K+-channel Slo-1 of nematodes and its interaction with emodepside","volume":"8","author":"D Kulke","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"10","key":"ppat.1009601.ref038","doi-asserted-by":"crossref","first-page":"e0004062","DOI":"10.1371\/journal.pntd.0004062","article-title":"The cyclooctadepsipeptide anthelmintic emodepside differentially modulates nematode, insect and human calcium-activated potassium (SLO) channel alpha subunits","volume":"9","author":"A Crisford","year":"2015","journal-title":"PLoS Negl Trop 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Kashyap","year":"2019","journal-title":"PLoS Pathog"},{"issue":"1\u20132","key":"ppat.1009601.ref045","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.molbiopara.2015.03.001","article-title":"Identification of novel splice variants of the voltage- and Ca(2)(+)-dependent K(+)-channel SLO-1 of Trichuris muris","volume":"199","author":"E Yilmaz","year":"2015","journal-title":"Mol Biochem Parasitol"},{"issue":"4","key":"ppat.1009601.ref046","doi-asserted-by":"crossref","first-page":"e1000380","DOI":"10.1371\/journal.ppat.1000380","article-title":"Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel","volume":"5","author":"L Rufener","year":"2009","journal-title":"PLoS Pathog"},{"key":"ppat.1009601.ref047","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molbiopara.2016.11.005","article-title":"WormBase ParaSite\u2014a comprehensive resource for helminth genomics","volume":"215","author":"KL 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