{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:50:07Z","timestamp":1791478207213,"version":"4.3.4"},"reference-count":59,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101019223"],"award-info":[{"award-number":["101019223"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Despite the enormous disease burden, treatments are limited for soil-transmitted helminthiasis. The handful of anthelmintic drugs suffer from variable and often insufficient efficacy against the pathogens. Resistance development, caused by high drug pressure, is an ongoing concern. New treatments are needed, and combination therapies may represent a promising therapeutic strategy. We explored emodepside as a partner in combination therapy and characterized drug-interaction effects with key anthelmintics\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      against different soil-transmitted helminths (STHs). Drug-interaction studies were carried out in human recombinant cytochromes P450 assays. Combination studies revealed species-, stage-, and drug-dependent interaction profiles. For benzimidazole-emodepside combinations, potentiation was only observed against\n                      <jats:italic toggle=\"yes\">Ancylostoma ceylanicum<\/jats:italic>\n                      larvae, while against adult stages, up to threefold potentiation or synergy (\u03a3FIC &lt; 0.9) was observed for\n                      <jats:italic toggle=\"yes\">Heligmosomoides polygyrus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Trichuris muris<\/jats:italic>\n                      , especially for albendazole and albendazole sulfoxide. Combinations of emodepside with macrocyclic lactones showed mostly strong synergy against\n                      <jats:italic toggle=\"yes\">H. polygyrus<\/jats:italic>\n                      larvae (\u03a3FIC 0.06\u20132.52), while other species trended toward antagonism (\u03a3FIC &gt;1.5). Against adult stages, potentiation or synergism was observed in\n                      <jats:italic toggle=\"yes\">H. polygyrus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">T. muris<\/jats:italic>\n                      , while against\n                      <jats:italic toggle=\"yes\">Strongyloides ratti<\/jats:italic>\n                      , only the moxidectin-emodepside combination was synergistic (\u03a3FIC 0.69\u20130.99). For nAChR agonists, levamisole showed the strongest effect against\n                      <jats:italic toggle=\"yes\">Necator americanus<\/jats:italic>\n                      larvae, while oxantel pamoate exhibited potentiation or synergistic effects across multiple species and life stages. CYP450 inhibition assays reveal no relevant drug-drug interactions. This study provides a thorough evaluation of emodepside as a combination partner against soil-transmitted helminths\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , paving the way for\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      studies and ultimately a novel combination therapy with emodepside against STH infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00825-26","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:51:46Z","timestamp":1791474706000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>In vitro<\/i>\n                    in-depth characterization of emodepside in combination with key anthelmintic drugs on soil-transmitted helminths"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5495-7952","authenticated-orcid":true,"given":"Anastasia","family":"Sch\u00e4rer","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Research, Swiss Tropical and Public Health Institute","place":["Allschwil, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Basel","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"H\u00e4berli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Research, Swiss Tropical and Public Health Institute","place":["Allschwil, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Basel","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Schlienger","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Research, Swiss Tropical and Public Health Institute","place":["Allschwil, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Basel","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0290-3521","authenticated-orcid":true,"given":"Jennifer","family":"Keiser","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03adhka07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Research, Swiss Tropical and Public Health Institute","place":["Allschwil, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Basel","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_3_5_2_2","unstructured":"World Health Organization. 2023. Soil-transmitted helminth infections. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/soil-transmitted-helminth-infections"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed4020073"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-81"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/RRTM.S278140"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-93364-z"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s44197-024-00231-7"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j4307"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5431491"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parepi.2024.e00370"},{"key":"e_1_3_5_11_2","unstructured":"World Health Organization. 2024. WHO guideline on preventive chemotherapy for public health control of strongyloidiasis. World Health Organization."},{"key":"e_1_3_5_12_2","unstructured":"World Health Organization. 2022. Ending the neglect to attain the sustainable development goals: a rationale for continued investment in tackling neglected tropical diseases 2021\u20132030. World Health Organization"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2022.2114829"},{"key":"e_1_3_5_14_2","unstructured":"Centers for Disease Control and Prevention. 2023. Parasites - strongyloides - resources for health professionals. Available from: https:\/\/www.cdc.gov\/parasites\/strongyloides\/health_professionals\/index.html#tx"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(10)73008-6"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(22)00331-7"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S103156"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idcr.2026.e02566"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2017.02.004"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.livsci.2018.09.022"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S332378"},{"key":"e_1_3_5_22_2","doi-asserted-by":"crossref","unstructured":"Rudrapal M Khairnar SJ Jadhav AG. 2020. Drug repurposing (DR): an emerging approach in drug discovery","DOI":"10.5772\/intechopen.93193"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-019-3476-x"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212825"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01403-X"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00255-5"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apar.2019.02.004"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apar.2018.08.002"},{"key":"e_1_3_5_29_2","first-page":"18","article-title":"Anthelmintics resistance; how to overcome it?","volume":"8","author":"Shalaby HA","year":"2013","unstructured":"Shalaby HA. 2013. Anthelmintics resistance; how to overcome it? Iran J Parasitol 8:18\u201332.","journal-title":"Iran J Parasitol"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00669-8"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00719"},{"key":"e_1_3_5_32_2","first-page":"1202","volume-title":"Manual of commercial methods in clinical microbiology","author":"Garcia LS","year":"2006","unstructured":"Garcia LS. 2006. Diagnostic medical parasitology, p 1202. In Manual of commercial methods in clinical microbiology, 5th ed. Amer Society for Microbiology.","edition":"5"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2023.10.001"},{"key":"e_1_3_5_34_2","unstructured":"Life Technologies. 2012. Vivid CYP450 screening kits user guide. Available from: https:\/\/assets.thermofisher.com\/TFS-Assets\/LSG\/manuals\/Vivid_CYP450_Screening_Kits_man.pdf"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057104269731"},{"key":"e_1_3_5_36_2","unstructured":"R Core Team. 2016. R: a language and environment for statistical computing. Vienna Austria R Foundation for Statistical Computing. https:\/\/www.r-project.org\/."},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.2c00581"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-332"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080790"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2022.10.002"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312808"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01217-16"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-002-0512-z"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2004.71.608"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-4758(90)90227-u"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01428.x"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01477-10"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12149"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2016.09.001"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70529-6"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15703"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003495"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2004.04.014"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000517"},{"key":"e_1_3_5_55_2","volume-title":"Early drug development: strategies and routes to first-in-human trials","author":"Cayen MN","year":"2011","unstructured":"Cayen MN. 2011. Early drug development: strategies and routes to first-in-human trials. John Wiley & Sons."},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-021-03025-z"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00762-18"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8AY00828K"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3992"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-023-05771-8"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00825-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00825-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:51:48Z","timestamp":1791474708000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00825-26"}},"subtitle":[],"editor":[{"given":"Cesar A.","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":59,"alternative-id":["10.1128\/aac.00825-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00825-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"2026-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00825-26"}}