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Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model.
Péricat, David; Leon-Icaza, Stephen Adonai; Sanchez Rico, Marina; Mühle, Christiane; Zoicas, Iulia; Schumacher, Fabian; Planès, Rémi; Mazars, Raoul; Gros, Germain; Carpinteiro, Alexander; Becker, Katrin Anne; Izopet, Jacques; Strub-Wourgaft, Nathalie; Sjö, Peter; Neyrolles, Olivier; Kleuser, Burkhard; Limosin, Frédéric; Gulbins, Erich; Kornhuber, Johannes; Meunier, Etienne; Hoertel, Nicolas; Cougoule, Céline.
  • Péricat D; Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France.
  • Leon-Icaza SA; Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France.
  • Sanchez Rico M; Faculté de Santé, Université Paris Cité, 75006 Paris, France.
  • Mühle C; Département de Psychiatrie et d'Addictologie de l'Adulte et du Sujet Agé, Assistance Publique-Hôpitaux de Paris (AP-HP), DMU Psychiatrie et Addictologie, Hôpital Corentin-Celton, 92130 Issy-les-Moulineaux, France.
  • Zoicas I; INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, 75014 Paris, France.
  • Schumacher F; Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
  • Planès R; Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
  • Mazars R; Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2-4, 14195 Berlin, Germany.
  • Gros G; Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France.
  • Carpinteiro A; Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France.
  • Becker KA; Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France.
  • Izopet J; Institute for Molecular Biology, University Medicine Essen, University of Duisburg-Essen, 47057 Essen, Germany.
  • Strub-Wourgaft N; Institute for Molecular Biology, University Medicine Essen, University of Duisburg-Essen, 47057 Essen, Germany.
  • Sjö P; Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), Université Toulouse, CNRS, INSERM, UPS, 31300 Toulouse, France.
  • Neyrolles O; Laboratoire de Virologie, CHU Toulouse, Hôpital Purpan, 31300 Toulouse, France.
  • Kleuser B; Drugs for Neglected Diseases Initiative, 1202 Geneva, Switzerland.
  • Limosin F; Drugs for Neglected Diseases Initiative, 1202 Geneva, Switzerland.
  • Gulbins E; Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31000 Toulouse, France.
  • Kornhuber J; Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2-4, 14195 Berlin, Germany.
  • Meunier E; Faculté de Santé, Université Paris Cité, 75006 Paris, France.
  • Hoertel N; Département de Psychiatrie et d'Addictologie de l'Adulte et du Sujet Agé, Assistance Publique-Hôpitaux de Paris (AP-HP), DMU Psychiatrie et Addictologie, Hôpital Corentin-Celton, 92130 Issy-les-Moulineaux, France.
  • Cougoule C; INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, 75014 Paris, France.
Int J Mol Sci ; 23(21)2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2099581
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world's 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, TNFα, 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 160/Cer 160 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: Ijms232113623

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: Ijms232113623