{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:55:44Z","timestamp":1793879744325,"version":"4.7.0"},"reference-count":75,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"ANR RA-COVID-19","doi-asserted-by":"publisher","award":["ANR-20-COV8-0008-20"],"award-info":[{"award-number":["ANR-20-COV8-0008-20"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"ANR RA-COVID-19","doi-asserted-by":"publisher","award":["N RF20210502852\/1\/1\/48"],"award-info":[{"award-number":["N RF20210502852\/1\/1\/48"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Toulouse Tech Transfer (OrganoCOVID)","award":["ANR-20-COV8-0008-20"],"award-info":[{"award-number":["ANR-20-COV8-0008-20"]}]},{"name":"Toulouse Tech Transfer (OrganoCOVID)","award":["N RF20210502852\/1\/1\/48"],"award-info":[{"award-number":["N RF20210502852\/1\/1\/48"]}]},{"name":"\u201cFondation pour la Recherche M\u00e9dicale\u201d (FRM) and ERC StG (INFLAME)","award":["ANR-20-COV8-0008-20"],"award-info":[{"award-number":["ANR-20-COV8-0008-20"]}]},{"name":"\u201cFondation pour la Recherche M\u00e9dicale\u201d (FRM) and ERC StG (INFLAME)","award":["N RF20210502852\/1\/1\/48"],"award-info":[{"award-number":["N RF20210502852\/1\/1\/48"]}]},{"name":"\u201cVaincre La Mucoviscidose\u201d PhD fellowship","award":["ANR-20-COV8-0008-20"],"award-info":[{"award-number":["ANR-20-COV8-0008-20"]}]},{"name":"\u201cVaincre La Mucoviscidose\u201d PhD fellowship","award":["N RF20210502852\/1\/1\/48"],"award-info":[{"award-number":["N RF20210502852\/1\/1\/48"]}]},{"name":"DFG research training group 2581","award":["ANR-20-COV8-0008-20"],"award-info":[{"award-number":["ANR-20-COV8-0008-20"]}]},{"name":"DFG research training group 2581","award":["N RF20210502852\/1\/1\/48"],"award-info":[{"award-number":["N RF20210502852\/1\/1\/48"]}]},{"name":"Federal Ministry of Education and Research (BMBF)","award":["ANR-20-COV8-0008-20"],"award-info":[{"award-number":["ANR-20-COV8-0008-20"]}]},{"name":"Federal Ministry of Education and Research (BMBF)","award":["N RF20210502852\/1\/1\/48"],"award-info":[{"award-number":["N RF20210502852\/1\/1\/48"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world\u2019s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase\/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNF\u03b1, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0\/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms232113623","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T11:56:36Z","timestamp":1667908596000},"page":"13623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model"],"prefix":"10.3390","volume":"23","author":[{"given":"David","family":"P\u00e9ricat","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7546-8228","authenticated-orcid":false,"given":"Stephen Adonai","family":"Leon-Icaza","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sanchez Rico","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Sant\u00e9, Universit\u00e9 Paris Cit\u00e9, 75006 Paris, France"},{"name":"D\u00e9partement de Psychiatrie et d\u2019Addictologie de l\u2019Adulte et du Sujet Ag\u00e9, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), DMU Psychiatrie et Addictologie, H\u00f4pital Corentin-Celton, 92130 Issy-les-Moulineaux, France"},{"name":"INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7517-9154","authenticated-orcid":false,"given":"Christiane","family":"M\u00fchle","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7187-3181","authenticated-orcid":false,"given":"Iulia","family":"Zoicas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8703-3275","authenticated-orcid":false,"given":"Fabian","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Str. 2-4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8612-3065","authenticated-orcid":false,"given":"R\u00e9mi","family":"Plan\u00e8s","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Mazars","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germain","family":"Gros","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1888-9595","authenticated-orcid":false,"given":"Burkhard","family":"Kleuser","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Str. 2-4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Limosin","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de Sant\u00e9, Universit\u00e9 Paris Cit\u00e9, 75006 Paris, France"},{"name":"D\u00e9partement de Psychiatrie et d\u2019Addictologie de l\u2019Adulte et du Sujet Ag\u00e9, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), DMU Psychiatrie et Addictologie, H\u00f4pital Corentin-Celton, 92130 Issy-les-Moulineaux, France"},{"name":"INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, 75014 Paris, 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