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If untreated, the disease can cause life-threatening complications. The current treatment of schistosomiasis relies on a single drug, praziquantel (PZQ). However, there is increasing concern about emerging resistance to  PZQ due to its frequent use.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>To identify potential alternative drugs for repurposing, the Open Global Health Library (OGHL) was screened in vitro, using two different screening workflows at two institutions, against adult <jats:italic>S. mansoni<\/jats:italic> couples and newly transformed schistosomula. This was followed by confirmation of the effects of the lead structures against adult worms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In vitro screening at one of the institutions identified two fast-acting substances affecting worm physiology (OGHL00022, OGHL00121). The effects of the two lead structures were investigated in more detail by confocal laser scanning microscopy and 5-ethynyl 2\u00b4-deoxyuridine (EdU) assays to assess morphological effects and stem cell effects. Both substances showed negative effects on stem cell proliferation in <jats:italic>S.\u00a0mansoni<\/jats:italic> but no further morphological changes. The EC<jats:sub>50<\/jats:sub>values of both compounds were determined, with values for compound OGHL00022 of 5.955\u00a0\u00b5M for pairing stability, 10.88\u00a0\u00b5M for attachment, and 18.77\u00a0\u00b5M for motility, while the values for compound OGHL00121 were 7.088\u00a0\u00b5M for pairing stability, 8.065\u00a0\u00b5M for attachment, and 6.297\u00a0\u00b5M for motility 24\u00a0h after treatment. Furthermore, <jats:italic>S. mansoni<\/jats:italic> couples were treated in vitro with these two lead structures simultaneously to check for additive effects, which were found with respect to reduced motility. The second in vitro screening, primarily against newly transformed schistosomula and secondarily against adult worms, identified four lead structures in total (OGHL00006, OGHL00022, OGHL00169, OGHL00217). In addition, one of the tested analogues of the hits OGHL00006, OGHL00169, and OGHL00217 showed effects on both stages.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In two independent in vitro screening approaches against two stages of <jats:italic>S. mansoni<\/jats:italic> one common interesting structure with rapid effects was identified, OGHL00022, which provides opportunities for further development.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s13071-024-06648-0","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T16:47:28Z","timestamp":1738687648000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Merck Open Global Health Library in vitro screening against Schistosoma mansoni identified two new substances with antischistosomal activities for further development"],"prefix":"10.1186","volume":"18","author":[{"given":"Monique Evelyn","family":"Ueberall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Berchthold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"H\u00e4berli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Lindemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Spangenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Keiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph G.","family":"Grevelding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"6648_CR1","unstructured":"World Health Organization. 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