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Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model

Published online by Cambridge University Press:  19 July 2023

D. Péricat ,
S. A. Leon-Icaza ,
M. Sánchez-Rico ,
C. Mühle ,
I. Zoicas ,
F. Schumacher ,
R. Planès ,
R. Mazars ,
G. Gros  and
A. Carpinteiro
...Show all authors
D. Péricat
Affiliation:
Institute of Pharmacology and Structural Biology (IPBS), Toulouse
S. A. Leon-Icaza
Affiliation:
Institute of Pharmacology and Structural Biology (IPBS), Toulouse
M. Sánchez-Rico
Affiliation:
Université Paris Cité, Paris, France
C. Mühle
Affiliation:
Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen
I. Zoicas
Affiliation:
Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen
F. Schumacher
Affiliation:
Freie Universität Berlin, Berlin
R. Planès
Affiliation:
Institute of Pharmacology and Structural Biology (IPBS), Toulouse
R. Mazars
Affiliation:
Institute of Pharmacology and Structural Biology (IPBS), Toulouse
G. Gros
Affiliation:
Institute of Pharmacology and Structural Biology (IPBS), Toulouse
A. Carpinteiro
Affiliation:
Institute for Molecular Biology, University Medicine Essen, Essen, Germany
K. A. Becker
Affiliation:
Institute for Molecular Biology, University Medicine Essen, Essen, Germany
J. Izopet
Affiliation:
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), Toulouse, France
N. Strub-Wourgaft
Affiliation:
Drugs for Neglected Diseases Initiative, Geneva, Switzerland
P. Sjö
Affiliation:
Drugs for Neglected Diseases Initiative, Geneva, Switzerland
O. Neyrolles
Affiliation:
Institute of Pharmacology and Structural Biology (IPBS), Toulouse
B. Kleuser
Affiliation:
Freie Universität Berlin, Berlin
F. Limosin
Affiliation:
Université Paris Cité, Paris, France
E. Gulbins
Affiliation:
Institute for Molecular Biology, University Medicine Essen, Essen, Germany
J. Kornhuber
Affiliation:
Institute for Molecular Biology, University Medicine Essen, Essen, Germany
E. Meunier
Affiliation:
Institute of Pharmacology and Structural Biology (IPBS), Toulouse
N. Hoertel*
Affiliation:
Université Paris Cité, Paris, France
C. Cougoule
Affiliation:
Institute of Pharmacology and Structural Biology (IPBS), Toulouse
*
*Corresponding author.

Abstract

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Introduction

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.

Objectives

The aim of this sudy was to test the potential antiviral and anti-inflammatory activities of fluoxetine against SARS-CoV-2 in a K18-hACE2 mouse model of infection, and against several variants of concern in vitro, and test the hypothesis of the implication of ceramides and/or their derivatives hexosylceramides.

Methods

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.

Results

Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres (Figure 1) and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10) (Figure 2). 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 (Figure 3).

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Image 2:

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Conclusions

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.

Disclosure of Interest

None Declared

Type
Abstract
Information
European Psychiatry , Volume 66 , Special Issue S1: Abstracts of the 31st European Congress of Psychiatry , March 2023 , pp. S119 - S120
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of the European Psychiatric Association
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