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

Carpinteiro A, Edwards MJ, Hoffmann M, Kochs G, Gripp B, Weigang S, Adams C, Carpinteiro E, Gulbins A, Keitsch S, Sehl C, Soddemann M, Wilker B, Kamler M, Bertsch T, Lang KS, Patel S, Wilson GC, Walter S, Hengel H, Pöhlmann S, Lang PA, Kornhuber J, Becker KA, Ahmad SA, Fassbender K, Gulbins E (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cell Reports Medicine Elsevier

Book Volume: 1

Article Number: 100142

Journal Issue: 8

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.

Authors with CRIS profile

Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) University of Cincinnati US United States (USA) (US) Deutsches Primatenzentrum (DPZ), Leibniz-Institut für Primatenforschung DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Paracelsus Medizinische Privatuniversität, Nürnberg DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Sana Kliniken AG DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE)

How to cite

APA:

Carpinteiro, A., Edwards, M.J., Hoffmann, M., Kochs, G., Gripp, B., Weigang, S.,... Gulbins, E. (2020). Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells. Cell Reports Medicine, 1(8). https://doi.org/10.1016/j.xcrm.2020.100142

MLA:

Carpinteiro, Alexander, et al. "Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells." Cell Reports Medicine 1.8 (2020).

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