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The acid sphingomyelinase/ceramide system in COVID-19
Johannes Kornhuber1, Nicolas Hoertel2,3, Erich Gulbins4,5
1Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany. johannes.kornhuber@uk-erlangen.de.
Molecular Psychiatry
|October 5, 2021
Summary
Acid sphingomyelinase (ASM) is crucial for SARS-CoV-2 entry by creating cell membrane platforms. Inhibiting ASM or blocking ceramide prevents infection, suggesting therapeutic potential for functional inhibitors of ASM (FIASMAs).
Area of Science:
- Biochemistry
- Virology
- Pharmacology
Background:
- Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin into ceramide, forming membrane platforms.
- SARS-CoV-2 utilizes these ceramide-rich platforms for cellular entry.
Purpose of the Study:
- To investigate the role of the ASM/ceramide system in SARS-CoV-2 infection.
- To evaluate the potential of ASM inhibitors as antiviral agents against COVID-19.
Main Methods:
- Investigated SARS-CoV-2 cell entry mechanisms.
- Assessed the impact of modulating ceramide levels and ASM activity on viral infection.
- Reviewed clinical data on functional inhibitors of acid sphingomyelinase (FIASMAs) in COVID-19 patients.
Main Results:
- SARS-CoV-2 infection depends on ASM-generated ceramide platforms.
- Inhibition of ASM, ceramide blockade, or degradation protected against SARS-CoV-2.
- Clinically approved FIASMAs, including fluvoxamine, fluoxetine, and hydroxyzine, demonstrated beneficial effects in COVID-19.
Conclusions:
- The ASM/ceramide pathway is a key target for SARS-CoV-2 entry.
- FIASMAs offer a promising therapeutic strategy for COVID-19, with potential antiviral and anti-inflammatory benefits.
- This framework supports drug repurposing and development for COVID-19 treatment.
