Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model
Pericat D, Leon-Icaza SA, Rico MS, Mühle C, Zoicas I, Schumacher F, Planes R, Mazars R, Gros G, Carpinteiro A, Becker KA, Izopet J, Strub-Wourgaft N, Sjoe P, Neyrolles O, Kleuser B, Limosin F, Gulbins E, Kornhuber J, Meunier E, Hoertel N, Cougoule C (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 23
Article Number: 13623
Journal Issue: 21
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 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.
Authors with CRIS profile
Christiane Mühle
Medizinische Fakultät
Iulia Zoicas
Department of Psychiatry and Psychotherapy
Johannes Kornhuber
Lehrstuhl für Psychiatrie und Psychotherapie
Involved external institutions
Université Fédérale de Toulouse Midi-Pyrénées
France (FR)
Freie Universität Berlin
Germany (DE)
Université de Paris
France (FR)
Universität Duisburg-Essen (UDE)
Germany (DE)
Drugs for Neglected Diseases initiative (DNDi)
Switzerland (CH)
France (FR)
Freie Universität Berlin
Germany (DE)
Université de Paris
France (FR)
Universität Duisburg-Essen (UDE)
Germany (DE)
Drugs for Neglected Diseases initiative (DNDi)
Switzerland (CH)
How to cite
APA:
Pericat, D., Leon-Icaza, S.A., Rico, M.S., Mühle, C., Zoicas, I., Schumacher, F.,... Cougoule, C. (2022). Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model. International Journal of Molecular Sciences, 23(21). https://doi.org/10.3390/ijms232113623
MLA:
Pericat, David, et al. "Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model." International Journal of Molecular Sciences 23.21 (2022).
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