Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants
Laura Thümmler,
Nadine Beckmann,
Carolin Sehl,
Matthias Soddemann,
Peer Braß,
Maren Bormann,
Leonie Brochhagen,
Carina Elsner,
Nicolas Hoertel,
Céline Cougoule,
Sandra Ciesek,
Marek Widera,
Ulf Dittmer,
Monika Lindemann,
Peter A. Horn,
Oliver Witzke,
Stephanie Kadow,
Markus Kamler,
Erich Gulbins,
Katrin Anne Becker,
Adalbert Krawczyk
Affiliations
Laura Thümmler
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Nadine Beckmann
Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Carolin Sehl
Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Matthias Soddemann
Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Peer Braß
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Maren Bormann
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Leonie Brochhagen
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Carina Elsner
Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Nicolas Hoertel
Institute Psychiatry and Neuroscience de Paris, INSERM U1266, Paris Cité University, 75014 Paris, France
Céline Cougoule
Institute of Pharmacology and Structural Biology (IPBS), CNRS, University of Toulouse, UPS, 31000 Toulouse, France
Sandra Ciesek
Institute of Medical Virology, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany
Marek Widera
Institute of Medical Virology, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany
Ulf Dittmer
Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Monika Lindemann
Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Peter A. Horn
Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Oliver Witzke
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Stephanie Kadow
Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Markus Kamler
Department of Thoracic and Cardiovascular Surgery, West German Heart Center, University Hospital Essen, 45147 Essen, Germany
Erich Gulbins
Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Katrin Anne Becker
Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Adalbert Krawczyk
Department of Infectious Diseases, West German Centre of Infectious Diseases, University Medicine Essen, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
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 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.
