puc-header

Inhibition of Acid Sphingomyelinase Blocks Infection with SARS-CoV-2

49 Pages Posted: 10 Jul 2020 Publication Status: Published

See all articles by Alexander Carpinteiro

Alexander Carpinteiro

University of Duisburg-Essen - Institute of Molecular Biology

Michael J. Edwards

University of Cincinnati - Department of Surgery

Markus Hoffmann

German Primate Center - Leibniz Institute for Primate Research

Georg Kochs

University of Freiburg - Faculty of Medicine

Barbara Gripp

Sana-Klinikum Remscheid GmbH - Zentrum für Seelische Gesundheit des Kindes- und Jugendalters

Sebastian Weigang

University of Freiburg - Faculty of Medicine

Constantin Adams

University of Tuebingen - Department of Pediatrics

Elisa Carpinteiro

University of Duisburg-Essen - Institute of Molecular Biology

Anne Gulbins

University of Duisburg-Essen - Institute of Molecular Biology

Simone Keitsch

University of Duisburg-Essen - Institute of Molecular Biology

Carolin Sehl

University of Duisburg-Essen - Institute of Molecular Biology

Matthias Soddemann

University of Duisburg-Essen - Institute of Molecular Biology

Barbara Wilker

University of Duisburg-Essen - Institute of Molecular Biology

Markus Kamler

University of Duisburg-Essen - Department of Thoracic and Cardiovascular Surgery

Thomas Bertsch

Paracelsus Medical University - Institute of Clinical Chemistry

Karl S. Lang

University of Duisburg-Essen - Institute of Immunology

Sameer Patel

University of Cincinnati - Department of Surgery

Gregory C. Wilson

University of Cincinnati - Department of Surgery

Silke Walter

Saarland University - Department of Neurology

Hartmut Hengel

University of Freiburg - Faculty of Medicine

Stefan Pöhlmann

German Primate Center - Leibniz Institute for Primate Research

Philipp Lang

Heinrich Heine University Dusseldorf - Department of Molecular Medicine II

Johannes Kornhuber

University of Erlangen-Nuremberg-Friedrich Alexander Universität Erlangen Nürnberg

Katrin Anne Becker

University of Duisburg-Essen - Institute of Molecular Biology

Syed A. Ahmad

University of Cincinnati - Department of Surgery

Klaus Fassbender

Saarland University - Department of Neurology

Erich Gulbins

University of Cincinnati - Department of Surgery

More...

Abstract

We have previously shown that the acid sphingomyelinase/ceramide system plays an important role in bacterial and viral infections. Pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram or maprotiline or genetic down-regulation of the enzyme prevents infection with authentic SARS-CoV-2 or pseudoviral particles expressing pp-VSV-SARS-CoV-2 spike that served as a bona fide system mimicking SARS-CoV-2 infection. Mechanistically, acid sphingomyelinase mediates the formation of ceramide-enriched membrane platforms that serve the infection with pp-VSV-SARS-CoV-2 spike. Neutralization or consumption of surface ceramide reduces infection with pp-VSV-SARS-CoV-2 spike. Treatment of volunteers with a low dose of amitriptyline prevents infection of freshly isolated nasal epithelial cells with pp-VSV-SARS-CoV-2 spike, indicating that amitriptyline can be repurposed to prevent SARS-CoV-2 infection. Our data suggest the use of amitriptyline, a safe drug clinically used for almost 60 years, other antidepressants blocking the acid sphingomyelinase, anti-ceramide antibodies and neutral ceramidase for prophylaxis and treatment of coronavirus disease-19.

Funding: The study was supported by DFG grant Gu-335-35/1 and BMBF, RAPID Consortium,
grant 01KI1723D to SP.

Conflict of Interest: The authors declare no competing financial interests.

Ethical Approval: The experiments were approved by the local ethics committee under the number 20-9348-BO.

Suggested Citation

Carpinteiro, Alexander and Edwards, Michael J. and Hoffmann, Markus and Kochs, Georg and Gripp, Barbara and Weigang, Sebastian and Adams, Constantin and Carpinteiro, Elisa and Gulbins, Anne and Keitsch, Simone and Sehl, Carolin and Soddemann, Matthias and Wilker, Barbara and Kamler, Markus and Bertsch, Thomas and Lang, Karl S. and Patel, Sameer and Wilson, Gregory C. and Walter, Silke and Hengel, Hartmut and Pöhlmann, Stefan and Lang, Philipp and Kornhuber, Johannes and Becker, Katrin Anne and Ahmad, Syed A. and Fassbender, Klaus and Gulbins, Erich, Inhibition of Acid Sphingomyelinase Blocks Infection with SARS-CoV-2. Available at SSRN: https://ssrn.com/abstract=3646562 or http://dx.doi.org/10.2139/ssrn.3646562
This version of the paper has not been formally peer reviewed.

Alexander Carpinteiro

University of Duisburg-Essen - Institute of Molecular Biology ( email )

Germany

Michael J. Edwards

University of Cincinnati - Department of Surgery ( email )

Cincinnati, OH
United States

Markus Hoffmann

German Primate Center - Leibniz Institute for Primate Research ( email )

Georg Kochs

University of Freiburg - Faculty of Medicine ( email )

Fahnenbergplatz
Freiburg, D-79085
Germany

Barbara Gripp

Sana-Klinikum Remscheid GmbH - Zentrum für Seelische Gesundheit des Kindes- und Jugendalters ( email )

Sebastian Weigang

University of Freiburg - Faculty of Medicine ( email )

Fahnenbergplatz
Freiburg, D-79085
Germany

Constantin Adams

University of Tuebingen - Department of Pediatrics ( email )

Tübingen
Germany

Elisa Carpinteiro

University of Duisburg-Essen - Institute of Molecular Biology ( email )

Germany

Anne Gulbins

University of Duisburg-Essen - Institute of Molecular Biology ( email )

Germany

Simone Keitsch

University of Duisburg-Essen - Institute of Molecular Biology ( email )

Germany

Carolin Sehl

University of Duisburg-Essen - Institute of Molecular Biology ( email )

Germany

Matthias Soddemann

University of Duisburg-Essen - Institute of Molecular Biology ( email )

Germany

Barbara Wilker

University of Duisburg-Essen - Institute of Molecular Biology ( email )

Germany

Markus Kamler

University of Duisburg-Essen - Department of Thoracic and Cardiovascular Surgery ( email )

Lotharstrasse 1
Duisburg, 47048
Germany

Thomas Bertsch

Paracelsus Medical University - Institute of Clinical Chemistry ( email )

Nürnberg
Germany

Karl S. Lang

University of Duisburg-Essen - Institute of Immunology ( email )

Lotharstrasse 1
Duisburg, 47048
Germany

Sameer Patel

University of Cincinnati - Department of Surgery ( email )

Cincinnati, OH
United States

Gregory C. Wilson

University of Cincinnati - Department of Surgery ( email )

Cincinnati, OH
United States

Silke Walter

Saarland University - Department of Neurology ( email )

Stadtwald
Saarbrucken, Saarland D-66123
Germany

Hartmut Hengel

University of Freiburg - Faculty of Medicine ( email )

Fahnenbergplatz
Freiburg, D-79085
Germany

Stefan Pöhlmann

German Primate Center - Leibniz Institute for Primate Research ( email )

Philipp Lang

Heinrich Heine University Dusseldorf - Department of Molecular Medicine II ( email )

Universitätsstrasse 1
Duesseldorf, DE NRW 40225
Germany

Johannes Kornhuber

University of Erlangen-Nuremberg-Friedrich Alexander Universität Erlangen Nürnberg

Schloßplatz 4
Erlangen, DE Bavaria 91054
Germany

Katrin Anne Becker

University of Duisburg-Essen - Institute of Molecular Biology ( email )

Germany

Syed A. Ahmad

University of Cincinnati - Department of Surgery ( email )

Cincinnati, OH
United States

Klaus Fassbender

Saarland University - Department of Neurology ( email )

Stadtwald
Saarbrucken, Saarland D-66123
Germany

Erich Gulbins (Contact Author)

University of Cincinnati - Department of Surgery ( email )

Click here to go to Cell.com

Paper statistics

Downloads
41
Abstract Views
2,413
PlumX Metrics