Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants

Laura Thümmler
,
Nadine Beckmann
,
Caroline Sehl
,
Matthias Soddemann
,
Peer Braß
ORCID logo ,
Maren Bormann
ORCID logo ,
Leonie Brochhagen
,
Carina Elsner
,
Nicolas Hoertel
,
Céline Cougoule
ORCID logo ,
Sandra Ciesek
,
Marek Widera
,
Ulf Dittmer
,
Monika Lindemann
ORCID logo ,
Peter A. Horn
,
Oliver Witzke
,
Stephanie Kadow
,
Markus Kamler
ORCID logo ,
Erich Gulbins
,
Katrin Anne Becker
ORCID logo ,
Adalbert Krawczyk
* ORCID logo
Version 1 : Received: 3 March 2024 / Approved: 4 March 2024 / Online: 4 March 2024 (19:12:30 CET)

A peer-reviewed article of this Preprint also exists.

Thümmler, L.; Beckmann, N.; Sehl, C.; Soddemann, M.; Braß, P.; Bormann, M.; Brochhagen, L.; Elsner, C.; Hoertel, N.; Cougoule, C.; Ciesek, S.; Widera, M.; Dittmer, U.; Lindemann, M.; Horn, P.A.; Witzke, O.; Kadow, S.; Kamler, M.; Gulbins, E.; Becker, K.A.; Krawczyk, A. Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants. Viruses 2024, 16, 545. Thümmler, L.; Beckmann, N.; Sehl, C.; Soddemann, M.; Braß, P.; Bormann, M.; Brochhagen, L.; Elsner, C.; Hoertel, N.; Cougoule, C.; Ciesek, S.; Widera, M.; Dittmer, U.; Lindemann, M.; Horn, P.A.; Witzke, O.; Kadow, S.; Kamler, M.; Gulbins, E.; Becker, K.A.; Krawczyk, A. Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants. Viruses 2024, 16, 545.

Abstract

The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase (FIASMA) against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.

Keywords

SARS-CoV-2; antidepressants, COVID-19

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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