The acid sphingomyelinase/ceramide system in COVID-19

Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, gene...

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Veröffentlicht in:Molecular psychiatry 2022-01, Vol.27 (1), p.307-314
Hauptverfasser: Kornhuber, Johannes, Hoertel, Nicolas, Gulbins, Erich
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Hoertel, Nicolas
Gulbins, Erich
description Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, genetic downregulation of ASM, anti-ceramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2. The addition of ceramide restored infection with SARS-CoV-2. Many clinically approved medications functionally inhibit ASM and are called FIASMAs (functional inhibitors of acid sphingomyelinase). The FIASMA fluvoxamine showed beneficial effects on COVID-19 in a randomized prospective study and a prospective open-label real-world study. Retrospective and observational studies showed favorable effects of FIASMA antidepressants including fluoxetine, and the FIASMA hydroxyzine on the course of COVID-19. The ASM/ceramide system provides a framework for a better understanding of the infection of cells by SARS-CoV-2 and the clinical, antiviral, and anti-inflammatory effects of functional inhibitors of ASM. This framework also supports the development of new drugs or the repurposing of “old” drugs against COVID-19.
doi_str_mv 10.1038/s41380-021-01309-5
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Antidepressants
Antiviral agents
Behavioral Sciences
Biological Psychology
Ceramidase
Ceramide
Ceramides - metabolism
Coronaviruses
COVID-19
Drug development
Fluoxetine
Fluvoxamine
Humans
Infections
Inflammation
Lipophilic
Medicine
Medicine & Public Health
Neurosciences
Pharmacotherapy
Prospective Studies
Psychiatry
Randomized Controlled Trials as Topic
Retrospective Studies
Review
Review Article
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Sphingomyelin
Sphingomyelin phosphodiesterase
Sphingomyelin Phosphodiesterase - genetics
title The acid sphingomyelinase/ceramide system in COVID-19
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