{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T20:51:39Z","timestamp":1785617499183,"version":"3.56.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German-Israeli Project Cooperation of the German Research Foundation","award":["SCHE 1833\/7-1"],"award-info":[{"award-number":["SCHE 1833\/7-1"]}]},{"name":"German-Israeli Project Cooperation of the German Research Foundation","award":["SCHE 1833\/7-2"],"award-info":[{"award-number":["SCHE 1833\/7-2"]}]},{"name":"LOEWE Center DRUID of the Hessian Ministry for Science and Research, Art and Culture","award":["LOEWE Center DRUID, A2"],"award-info":[{"award-number":["LOEWE Center DRUID, A2"]}]},{"name":"LOEWE Center DRUID of the Hessian Ministry for Science and Research, Art and Culture","award":["LOEWE Center DRUID, A3"],"award-info":[{"award-number":["LOEWE Center DRUID, A3"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Arthropod-borne viruses cause major global health burdens, yet few vaccines or antivirals exist. Targeting host factors required for viral replication offers a promising approach. The DEAD-box RNA helicase eIF4A, a core component of the translation initiation complex eIF4F, unwinds structured 5\u2032 UTRs and is therefore critical also for the translation of many viral RNAs. The compound classes rocaglates and pateamines are potent eIF4A inhibitors in mammalian cells. Here we show that the natural rocaglate silvestrol strongly inhibits Rift Valley fever virus replication (RVFV) in human cells without cytotoxicity, expanding the list of eIF4A-dependent arboviruses. Moreover, we studied eIF4A function and rocaglate\/pateamine sensitivity in insects, specifically in the arboviral vector\n                    <jats:italic>Aedes aegypti<\/jats:italic>\n                    and the fruit flies\n                    <jats:italic>Anastrepha suspensa<\/jats:italic>\n                    and\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    . Sequence analysis showed conservation of the rocaglate-binding motif between the human eIF4A and all three insects. Dual luciferase assays in insect cell lines confirmed selective translation inhibition from purine-rich reporters by silvestrol below cytotoxic thresholds. Purified eIF4A variants from all three insect species retained helicase activity, allowing direct testing of inhibitor interactions. Thermal shift assays demonstrated robust stabilization of eIF4A\u2013RNA complexes by both compound classes in the wildtype proteins, with unexpected rocaglate sensitivity of the putatively insensitive\n                    <jats:italic>Ae. aegypti<\/jats:italic>\n                    H161L mutant, indicating a unique binding pocket geometry of the mosquito protein. In summary, our results present RVFV as another drug target for eIF4A inhibitors and highlight comparative biochemistry studies providing insights into distinctive eIF4A inhibitor binding site architecture, with the prospect of exploring informed design to develop species-specific inhibitors.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0346047","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T17:42:52Z","timestamp":1775497372000},"page":"e0346047","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The RNA helicase eIF4A as a novel target in insect cells to combat arboviral infections"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4173-9816","authenticated-orcid":true,"given":"Tanja","family":"Rehling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Mentchen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Konopka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Obermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedemann","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Schmerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9217-394X","authenticated-orcid":true,"given":"Marc 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