The acid sphingomyelinase/ceramide system in COVID-19.
Mol Psychiatry
; 27(1): 307-314, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1450276
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sphingomyelin Phosphodiesterase
/
COVID-19
Type of study:
Cohort study
/
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Mol Psychiatry
Journal subject:
Molecular Biology
/
Psychiatry
Year:
2022
Document Type:
Article
Affiliation country:
S41380-021-01309-5
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