Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
International journal of molecular sciences - 23(2022), 21 vom: 07. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Péricat, David [VerfasserIn] |
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| Links: |
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| Themen: |
01K63SUP8D |
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| Anmerkungen: |
Date Completed 16.11.2022 Date Revised 06.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms232113623 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM348759959 |
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| 245 | 1 | 0 | |a Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a anti-depressant | |
| 650 | 4 | |a fluoxetine | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a mouse model | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
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| 700 | 1 | |a Leon-Icaza, Stephen Adonai |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez Rico, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Mühle, Christiane |e verfasserin |4 aut | |
| 700 | 1 | |a Zoicas, Iulia |e verfasserin |4 aut | |
| 700 | 1 | |a Schumacher, Fabian |e verfasserin |4 aut | |
| 700 | 1 | |a Planès, Rémi |e verfasserin |4 aut | |
| 700 | 1 | |a Mazars, Raoul |e verfasserin |4 aut | |
| 700 | 1 | |a Gros, Germain |e verfasserin |4 aut | |
| 700 | 1 | |a Carpinteiro, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Becker, Katrin Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Izopet, Jacques |e verfasserin |4 aut | |
| 700 | 1 | |a Strub-Wourgaft, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Sjö, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Neyrolles, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Kleuser, Burkhard |e verfasserin |4 aut | |
| 700 | 1 | |a Limosin, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Gulbins, Erich |e verfasserin |4 aut | |
| 700 | 1 | |a Kornhuber, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Meunier, Etienne |e verfasserin |4 aut | |
| 700 | 1 | |a Hoertel, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Cougoule, Céline |e verfasserin |4 aut | |
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