{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:49:48Z","timestamp":1790243388584,"version":"4.1.0"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008769","name":"Julius-Maximilians-Universit\u00e4t W\u00fcrzburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008769","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications \"off-label\" against SARS-CoV-2. Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8\u00a0\u00b5g\/ml significantly in these screenings, and the EC50 was determined with 387\u00a0ng\/ml. Furthermore, Fluoxetine reduced viral infectivity in precision-cut human lung slices showing its activity in relevant human tissue targeted in severe infections. Fluoxetine treatment resulted in a decrease in viral protein expression. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus, indicating that the R-form might specifically be used for SARS-CoV-2 treatment. Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. Moreover, since it is known that Fluoxetine inhibits cytokine release, we see the role of Fluoxetine in the treatment of SARS-CoV-2 infected patients of risk groups.<\/jats:p>","DOI":"10.1038\/s41598-021-85049-0","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T07:03:41Z","timestamp":1615791821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in human lung tissue"],"prefix":"10.1038","volume":"11","author":[{"given":"Melissa","family":"Zimniak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Kirschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Hilpert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Geiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Danov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Oberwinkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Steinke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Sewald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Seibel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Bodem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"85049_CR1","first-page":"2","volume":"2","author":"JD Goldman","year":"2020","unstructured":"Goldman, J. D. et al. Remdesivir for 5 or 10 days in patients with severe Covid-19. N. Engl. J. Med. 2, 2 (2020).","journal-title":"N. Engl. J. Med."},{"key":"85049_CR2","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1056\/NEJMoa2001282","volume":"382","author":"B Cao","year":"2020","unstructured":"Cao, B. et al. A trial of lopinavir-ritonavir in adults hospitalised with severe covid-19. N. Engl. J. Med. 382, 1787\u20131799 (2020).","journal-title":"N. Engl. J. Med."},{"key":"85049_CR3","doi-asserted-by":"publisher","first-page":"m1432","DOI":"10.1136\/bmj.m1432","volume":"369","author":"RE Ferner","year":"2020","unstructured":"Ferner, R. E. & Aronson, J. K. Chloroquine and hydroxychloroquine in covid-19. BMJ 369, m1432 (2020).","journal-title":"BMJ"},{"key":"85049_CR4","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1001\/jama.2020.16349","volume":"324","author":"CD Spinner","year":"2020","unstructured":"Spinner, C. D. et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: A randomised clinical trial. JAMA 324, 1048\u20131057 (2020).","journal-title":"JAMA"},{"key":"85049_CR5","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1016\/S0140-6736(20)31042-4","volume":"395","author":"IFN Hung","year":"2020","unstructured":"Hung, I. F. N. et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: An open-label, randomised, phase 2 trial. Lancet 395, 1695\u20131704 (2020).","journal-title":"Lancet"},{"key":"85049_CR6","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41422-020-0282-0","volume":"30","author":"M Wang","year":"2020","unstructured":"Wang, M. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30, 269\u2013271 (2020).","journal-title":"Cell Res."},{"key":"85049_CR7","first-page":"2","volume":"2","author":"A Gerard","year":"2020","unstructured":"Gerard, A. et al. \u201cOff-label\u201d use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: A survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers. Therapie 2, 2 (2020).","journal-title":"Therapie"},{"key":"85049_CR8","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1056\/NEJM199411173312008","volume":"331","author":"GL Fluoxetine","year":"1994","unstructured":"Fluoxetine, G. L. N. Engl. J. Med. 331, 1354\u20131361 (1994).","journal-title":"N. Engl. J. Med."},{"key":"85049_CR9","first-page":"2","volume":"2","author":"V Neuhaus","year":"2018","unstructured":"Neuhaus, V. et al. Assessment of the cytotoxic and immunomodulatory effects of substances in human precision-cut lung slices. J. Vis. Exp. 2, 2 (2018).","journal-title":"J. Vis. Exp."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85049-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85049-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85049-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T00:18:12Z","timestamp":1670026692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85049-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,15]]},"references-count":9,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["85049"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-85049-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.14.150490","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,15]]},"assertion":[{"value":"5 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"JB has been funded by Novartis, and other authors do not have any competing interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5890"}}