2. Academic Validation
  3. Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells

Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells

  • Cell Rep Med. 2020 Nov 17;1(8):100142. doi: 10.1016/j.xcrm.2020.100142.
Alexander Carpinteiro 1 2,  Michael J Edwards 3,  Markus Hoffmann 4 5,  Georg Kochs 6,  Barbara Gripp 7,  Sebastian Weigang 6,  Constantin Adams 8,  Elisa Carpinteiro 1,  Anne Gulbins 1,  Simone Keitsch 1,  Carolin Sehl 1,  Matthias Soddemann 1,  Barbara Wilker 1,  Markus Kamler 9,  Thomas Bertsch 10,  Karl S Lang 11,  Sameer Patel 3,  Gregory C Wilson 3,  Silke Walter 12,  Hartmut Hengel 6,  Stefan Pöhlmann 4 5,  Philipp A Lang 13,  Johannes Kornhuber 14,  Katrin Anne Becker 1,  Syed A Ahmad 3,  Klaus Fassbender 12,  Erich Gulbins 1 3
Affiliations

Affiliations

  • 1 Institute of Molecular Biology, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
  • 2 Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
  • 3 Department of Surgery, University of Cincinnati Medical School, 231 Albert Sabin Way, ML0558, Cincinnati, OH 45267, USA.
  • 4 Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.
  • 5 Faculty of Biology and Psychology, University of Göttingen, 37073 Göttingen, Germany.
  • 6 Institute of Virology and Faculty of Medicine, University of Freiburg, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany.
  • 7 Zentrum für Seelische Gesundheit des Kindes- und Jugendalters, Sana-Klinikum Remscheid GmbH, Burger Strasse 211, 42859 Remscheid, Germany.
  • 8 Department of Paediatrics, University Hospital Tuebingen, 72076 Tuebingen, Germany.
  • 9 Department of Thoracic and Cardiovascular Surgery, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
  • 10 Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Paracelsus Medical University, Nuremberg, Germany.
  • 11 Institute of Immunology, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany.
  • 12 Department of Neurology, University Hospital of the Saarland, Kirrberger Strasse, 66421 Homburg/Saar, Germany.
  • 13 Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitaetsstrasse 1, 40225 Düsseldorf, Germany.
  • 14 Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, 91054 Erlangen, Germany.
PMID: 33163980 DOI: 10.1016/j.xcrm.2020.100142
Abstract

The acid sphingomyelinase/ceramide system plays an important role in Bacterial and viral infections. Here, we report that either pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram, or maprotiline or genetic downregulation of the Enzyme prevents Infection of cultured cells or freshy isolated human nasal epithelial cells with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vesicular stomatitis virus (VSV) pseudoviral particles (pp-VSV) presenting SARS-CoV-2 spike protein (pp-VSV-SARS-CoV-2 spike), a bona fide system mimicking SARS-CoV-2 Infection. Infection activates acid sphingomyelinase and triggers a release of ceramide on the cell surface. Neutralization or consumption of surface ceramide reduces Infection with pp-VSV-SARS-CoV-2 spike. Treating volunteers with a low dose of amitriptyline prevents Infection of freshly isolated nasal epithelial cells with pp-VSV-SARS-CoV-2 spike. The data justify clinical studies investigating whether amitriptyline, a safe drug used clinically for almost 60 years, or other antidepressants that functionally block acid sphingomyelinase prevent SARS-CoV-2 Infection.

Keywords

SARS-CoV-2; acid sphingomyelinase; amitriptyline; antidepressants; ceramide; escitalopram; fluoxetine; human nasal epithelial cells; infection.

Figures