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Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms.<\/jats:p>","DOI":"10.3390\/ph15060669","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T23:43:03Z","timestamp":1653867783000},"page":"669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-0408","authenticated-orcid":false,"given":"Anthony","family":"Marchand","sequence":"first","affiliation":[{"name":"Laboratory of Intestinal Immunology, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Van Bree","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathology, Alfred Medical Research and Education Precinct (AMREP), Monash University, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3489-4367","authenticated-orcid":false,"given":"Aya","family":"Taki","sequence":"additional","affiliation":[{"name":"Melbourne Veterinary School, The University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mati","family":"Moyat","sequence":"additional","affiliation":[{"name":"Laboratory of Intestinal Immunology, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland"},{"name":"Department of Immunology and Pathology, Alfred Medical Research and Education Precinct (AMREP), Monash University, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-223X","authenticated-orcid":false,"given":"Gerardo","family":"Turcatti","sequence":"additional","affiliation":[{"name":"Biomolecular Screening Facility, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Chambon","sequence":"additional","affiliation":[{"name":"Biomolecular Screening Facility, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4593-3042","authenticated-orcid":false,"given":"Adam","family":"Smith","sequence":"additional","affiliation":[{"name":"Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Doolan","sequence":"additional","affiliation":[{"name":"Hookworm Immuno-Biology Laboratory, Swiss Tropical and Public Health Institute, 4123 Allschwill, Switzerland"},{"name":"Basel University, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-1690","authenticated-orcid":false,"given":"Robin","family":"Gasser","sequence":"additional","affiliation":[{"name":"Melbourne Veterinary School, The University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-0210","authenticated-orcid":false,"given":"Nicola","family":"Harris","sequence":"additional","affiliation":[{"name":"Laboratory of Intestinal Immunology, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland"},{"name":"Department of Immunology and Pathology, Alfred Medical Research and Education Precinct (AMREP), Monash University, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Bouchery","sequence":"additional","affiliation":[{"name":"Laboratory of Intestinal Immunology, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland"},{"name":"Department of Immunology and Pathology, Alfred Medical Research and Education Precinct (AMREP), Monash University, Melbourne, VIC 3004, Australia"},{"name":"Hookworm Immuno-Biology Laboratory, Swiss Tropical and Public Health Institute, 4123 Allschwill, Switzerland"},{"name":"Basel University, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJMra032492","article-title":"Hookworm infection","volume":"351","author":"Hotez","year":"2004","journal-title":"N. 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