{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:13:14Z","timestamp":1790730794527,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 Research and Innovation Program","award":["848166"],"award-info":[{"award-number":["848166"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Program","award":["771883"],"award-info":[{"award-number":["771883"]}]},{"name":"European Research Council\u2019s Consolidator grant","award":["848166"],"award-info":[{"award-number":["848166"]}]},{"name":"European Research Council\u2019s Consolidator grant","award":["771883"],"award-info":[{"award-number":["771883"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza virus (IV) infections pose a burden on global public health with significant morbidity and mortality. The limited range of currently licensed IV antiviral drugs is susceptible to the rapid rise of resistant viruses. In contrast, FDA-approved kinase inhibitors can be repurposed as fast-tracked host-targeted antivirals with a higher barrier of resistance. Extending our recent studies, we screened 21 FDA-approved small-molecule kinase inhibitors (SMKIs) and identified seven candidates as potent inhibitors of pandemic and seasonal IV infections. These SMKIs were further validated in a biologically and clinically relevant ex vivo model of human precision-cut lung slices. We identified steps of the virus infection cycle affected by these inhibitors (entry, replication, egress) and found that most SMKIs affected both entry and egress. Based on defined and overlapping targets of these inhibitors, the candidate SMKIs target receptor tyrosine kinase (RTK)-mediated activation of Raf\/MEK\/ERK pathways to limit influenza A virus infection. Our data and the established safety profiles of these SMKIs support further clinical investigations and repurposing of these SMKIs as host-targeted influenza therapeutics.<\/jats:p>","DOI":"10.3390\/v14092058","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:08:09Z","timestamp":1663718889000},"page":"2058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["FDA-Approved Inhibitors of RTK\/Raf Signaling Potently Impair Multiple Steps of In Vitro and Ex Vivo Influenza A Virus Infections"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4191-8021","authenticated-orcid":false,"given":"Robert","family":"Meineke","sequence":"first","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine in Hannover (TiHo), B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8804-9092","authenticated-orcid":false,"given":"Sonja","family":"Stelz","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine in Hannover (TiHo), B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4682-3531","authenticated-orcid":false,"given":"Maximilian","family":"Busch","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine in Hannover (TiHo), B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7694-4257","authenticated-orcid":false,"given":"Christopher","family":"Werlein","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"K\u00fchnel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"},{"name":"Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover Medical School (MHH), Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-2281","authenticated-orcid":false,"given":"Danny","family":"Jonigk","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"},{"name":"Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover Medical School (MHH), Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1921-4581","authenticated-orcid":false,"given":"Guus F.","family":"Rimmelzwaan","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine in Hannover (TiHo), B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1243-0967","authenticated-orcid":false,"given":"Husni","family":"Elbahesh","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine in Hannover (TiHo), B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, January 11). 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