{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T08:08:45Z","timestamp":1772179725387,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011205","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N024842\/1"],"award-info":[{"award-number":["MR\/N024842\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["(CiC6) 2017 MC_PC_17180"],"award-info":[{"award-number":["(CiC6) 2017 MC_PC_17180"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Hundreds of millions of people worldwide are infected with the whipworm\n                    <jats:italic>Trichuris trichiura<\/jats:italic>\n                    . Novel treatments are urgently needed as current drugs, such as albendazole, have relatively low efficacy. We have investigated whether drugs approved for other human diseases could be repurposed as novel anti-whipworm drugs. In a previous comparative genomics analysis, we identified 409 drugs approved for human use that we predicted to target parasitic worm proteins. Here we tested these\n                    <jats:italic>ex vivo<\/jats:italic>\n                    by assessing motility of adult worms of\n                    <jats:italic>Trichuris muris<\/jats:italic>\n                    , the murine whipworm, an established model for human whipworm research. We identified 14 compounds with EC\n                    <jats:sub>50<\/jats:sub>\n                    values of\n                    <jats:bold>\u2264<\/jats:bold>\n                    50 \u03bcM against\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>muris ex vivo<\/jats:italic>\n                    , and selected nine for testing\n                    <jats:italic>in vivo<\/jats:italic>\n                    . However, the best worm burden reduction seen in mice was just 19%. The high number of\n                    <jats:italic>ex vivo<\/jats:italic>\n                    hits against\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>muris<\/jats:italic>\n                    shows that we were successful at predicting parasite proteins that could be targeted by approved drugs. In contrast, the low efficacy of these compounds in mice suggest challenges due to their chemical properties (e.g. lipophilicity, polarity, molecular weight) and pharmacokinetics (e.g. absorption, distribution, metabolism, and excretion) that may (i) promote absorption by the host gastrointestinal tract, thereby reducing availability to the worms embedded in the large intestine, and\/or (ii) restrict drug uptake by the worms. This indicates that identifying structural analogues that have reduced absorption by the host, and increased uptake by worms, may be necessary for successful drug development against whipworms.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0011205","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:31:02Z","timestamp":1693920662000},"page":"e0011205","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["A drug repurposing screen for whipworms informed by comparative genomics"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-5951","authenticated-orcid":true,"given":"Avril","family":"Coghlan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick 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