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A straightforward approach to speed up drug development at lower costs is drug repurposing. Here, we investigated the therapeutic potential of targeting the interface of SARS CoV\u20102 with the host via repurposing of clinically licensed drugs and evaluated their use in combinatory treatments with virus\u2010 and host\u2010directed drugs in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We tested the antiviral potential of the antifungal itraconazole and the antidepressant fluoxetine on the production of infectious SARS\u2010CoV\u20102 particles in the polarized Calu\u20103 cell culture model and evaluated the added benefit of a combinatory use of these host\u2010directed drugs with the direct acting antiviral remdesivir, an inhibitor of viral RNA polymerase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Drug treatments were well\u2010tolerated and potently impaired viral replication. Importantly, both itraconazole\u2013remdesivir and fluoxetine\u2013remdesivir combinations inhibited the production of infectious SARS\u2010CoV\u20102 particles\u2009&gt;\u200990% and displayed synergistic effects, as determined in commonly used reference models for drug interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Itraconazole\u2013remdesivir and fluoxetine\u2013remdesivir combinations are promising starting points for therapeutic options to control SARS\u2010CoV\u20102 infection and severe progression of COVID\u201019.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15418","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:31Z","timestamp":1617753631000},"page":"2339-2350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS\u2010CoV\u20102 infection in vitro"],"prefix":"10.1111","volume":"178","author":[{"given":"Sebastian","family":"Schloer","sequence":"first","affiliation":[{"name":"Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and \u201cCells in Motion\u201d Interfaculty Centre University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8074-7400","authenticated-orcid":false,"given":"Linda","family":"Brunotte","sequence":"additional","affiliation":[{"name":"Institute of Virology, Center for Molecular Biology of Inflammation, and \u201cCells in Motion\u201d Interfaculty Centre University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles","family":"Mecate\u2010Zambrano","sequence":"additional","affiliation":[{"name":"Institute of Virology, Center for Molecular Biology of Inflammation, and \u201cCells in Motion\u201d Interfaculty Centre University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Research Program in Systems Oncology, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-7710","authenticated-orcid":false,"given":"Jing","family":"Tang","sequence":"additional","affiliation":[{"name":"Research Program in Systems Oncology, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4490-3052","authenticated-orcid":false,"given":"Stephan","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Institute of Virology, Center for Molecular Biology of Inflammation, and \u201cCells in Motion\u201d Interfaculty Centre University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8892-319X","authenticated-orcid":false,"given":"Ursula","family":"Rescher","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, and \u201cCells in Motion\u201d Interfaculty Centre University of Muenster  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00221-18"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14752"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14753"},{"issue":"4","key":"e_1_2_13_5_1","first-page":"66","article-title":"Evaluation of posaconazole pharmacokinetics in adult patients with invasive fungal infection","volume":"5","author":"Allegra S.","year":"2017","journal-title":"Biomedicine"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010365557"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(20)30195\u2010X"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007764"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2019.104541"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20100691.2006.01611.x"},{"key":"e_1_2_13_12_1","unstructured":"Drugs.com [Internet].Drug Interaction Checker from Drugs.com; 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