dc.contributor.author
Pericat, D.
dc.contributor.author
Leon-Icaza, S. A.
dc.contributor.author
Sánchez-Rico, M.
dc.contributor.author
Mühle, C.
dc.contributor.author
Zoicas, I.
dc.contributor.author
Schumacher, Fabian
dc.contributor.author
Planes, R.
dc.contributor.author
Mazars, R.
dc.contributor.author
Gros, G.
dc.contributor.author
Kleuser, Burkhard
dc.date.accessioned
2023-11-15T12:20:32Z
dc.date.available
2023-11-15T12:20:32Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/41532
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-41251
dc.description.abstract
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).
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.
en
dc.format.extent
2 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1192/j.eurpsy.2023.318
dcterms.bibliographicCitation.journaltitle
European Psychiatry
dcterms.bibliographicCitation.number
S1
dcterms.bibliographicCitation.pagestart
S119
dcterms.bibliographicCitation.pageend
S120
dcterms.bibliographicCitation.volume
66
dcterms.bibliographicCitation.url
https://doi.org/10.1192/j.eurpsy.2023.318
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie

refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1778-3585
refubium.resourceType.provider
WoS-Alert