{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:54:31Z","timestamp":1788317671479,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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":["1981052"],"award-info":[{"award-number":["1981052"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Mosquito-borne viruses including dengue, Zika, and Chikungunya viruses, and parasites such as malaria and Onchocerca volvulus endanger health and economic security around the globe, and emerging mosquito-borne pathogens have pandemic potential. However, the rapid spread of insecticide resistance threatens our ability to control mosquito vectors. Larvae of Aedes aegypti were screened with the Medicines for Malaria Venture Pandemic Response Box, an open-source compound library, using INVAPP, an invertebrate automated phenotyping platform suited to high-throughput chemical screening of larval motility. We identified rubitecan (a synthetic derivative of camptothecin) as a hit compound that reduced A. aegypti larval motility. Both rubitecan and camptothecin displayed concentration dependent reduction in larval motility with estimated EC50 of 25.5 \u00b1 5.0 \u00b5M and 22.3 \u00b1 5.4 \u00b5M, respectively. We extended our investigation to adult mosquitoes and found that camptothecin increased lethality when delivered in a blood meal to A. aegypti adults at 100 \u00b5M and 10 \u00b5M, and completely blocked egg laying when fed at 100 \u00b5M. Camptothecin and its derivatives are inhibitors of topoisomerase I, have known activity against several agricultural pests, and are also approved for the treatment of several cancers. Crucially, they can inhibit Zika virus replication in human cells, so there is potential for dual targeting of both the vector and an important arbovirus that it carries.<\/jats:p>","DOI":"10.3390\/molecules26206226","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:05:47Z","timestamp":1634511947000},"page":"6226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-4297","authenticated-orcid":false,"given":"Frederick A.","family":"Partridge","sequence":"first","affiliation":[{"name":"Centre for Respiratory Biology, UCL Respiratory, Division of Medicine, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9831-5697","authenticated-orcid":false,"given":"Beth C.","family":"Poulton","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milly A. I.","family":"Lake","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Biology, UCL Respiratory, Division of Medicine, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Lees","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry-Jack","family":"Mann","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Biology, UCL Respiratory, Division of Medicine, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2422-053X","authenticated-orcid":false,"given":"Gareth J.","family":"Lycett","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Sattelle","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Biology, UCL Respiratory, Division of Medicine, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41586-019-1717-y","article-title":"A new twenty-first century science for effective epidemic response","volume":"575","author":"Bedford","year":"2019","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41564-018-0214-7","article-title":"Vector biology meets disease control: Using basic research to fight vector-borne diseases","volume":"4","author":"Shaw","year":"2019","journal-title":"Nat. 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