{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T17:03:31Z","timestamp":1761930211708,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G033618N and G013118N"],"award-info":[{"award-number":["G033618N and G013118N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007660","name":"Universiteit Antwerpen","doi-asserted-by":"publisher","award":["TT-ZAPBOF 33049"],"award-info":[{"award-number":["TT-ZAPBOF 33049"]}],"id":[{"id":"10.13039\/501100007660","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005357","name":"Agent\u00fara na Podporu V\u00fdskumu a V\u00fdvoja","doi-asserted-by":"publisher","award":["APVV-15-0604"],"award-info":[{"award-number":["APVV-15-0604"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.<\/jats:p>","DOI":"10.3390\/microorganisms9040826","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T22:55:09Z","timestamp":1618354509000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in Trypanosoma brucei"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3530-0567","authenticated-orcid":false,"given":"Dorien","family":"Mabille","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0207-0902","authenticated-orcid":false,"given":"Camila","family":"Cardoso Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"},{"name":"Laborat\u00f3rio de Biologia Celular (LBC), Instituto Oswaldo Cruz (IOC\/Fiocruz), Rio de Janeiro 21040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"Hendrickx","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6396-0963","authenticated-orcid":false,"given":"Mathieu","family":"Claes","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Takac","sequence":"additional","affiliation":[{"name":"Institute of Zoology, Slovak Academy of Sciences, 84506 Bratislava, Slovakia"},{"name":"Scientica, Ltd., 83106 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Clayton","sequence":"additional","affiliation":[{"name":"DKFZ-ZMBH Alliance, Zentrum f\u00fcr Molekulare Biologie der Universit\u00e4t Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1571-7296","authenticated-orcid":false,"given":"Sarah","family":"Hendrickx","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7470-3484","authenticated-orcid":false,"given":"Fabian","family":"Hulpia","sequence":"additional","affiliation":[{"name":"Laboratory for Medicinal Chemistry, Campus Heymans, Ghent University, 9000 Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-9509","authenticated-orcid":false,"given":"Louis","family":"Maes","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4201-1264","authenticated-orcid":false,"given":"Serge","family":"Van Calenbergh","sequence":"additional","affiliation":[{"name":"Laboratory for Medicinal Chemistry, Campus Heymans, Ghent University, 9000 Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4870-3202","authenticated-orcid":false,"given":"Guy","family":"Caljon","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S1474-4422(12)70296-X","article-title":"Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)","volume":"12","author":"Kennedy","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tirados, I., Esterhuizen, J., Kovacic, V., Mangwiro, T.N., Vale, G.A., Hastings, I., Solano, P., Lehane, M.J., and Torr, S.J. 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