Acid sphingomyelinase (ASM) and COVID-19: A review of the potential use of ASM inhibitors against SARS-CoV-2.
Cell Biochem Funct
; 41(3): 284-295, 2023 Apr.
Article
in English
| MEDLINE | ID: covidwho-2275936
ABSTRACT
In the last 2 years, different pharmacological agents have been indicated as potential inhibitors of SARS-CoV-2 in vitro. Specifically, drugs termed as functional inhibitors of acid sphingomyelinase (FIASMAs) have proved to inhibit the SARS-CoV-2 replication using different types of cells. Those therapeutic agents share several chemical structure characteristics and some well-known representatives are fluoxetine, escitalopram, fluvoxamine, and others. Most of the FIASMAs are primarily used as effective therapeutic agents to treat different pathologies, therefore, they are natural drug candidates for repositioning strategy. In this review, we summarize the two main proposed mechanisms mediating acid sphingomyelinase (ASM) inhibition and how they can explain the inhibition of SARS-CoV-2 replication by FIASMAs. The first mechanism implies a disruption in the lysosomal pH fall as the endosome-lysosome moves toward the interior of the cell. In fact, changes in cholesterol levels in endosome-lysosome membranes, which are associated with ASM inhibition is thought to be mediated by lysosomal proton pump (ATP-ase) inactivation. The second mechanism involves the formation of an extracellular ceramide-rich domain, which is blocked by FIASMAs. The ceramide-rich domains are believed to facilitate the SARS-CoV-2 entrance into the host cells.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sphingomyelin Phosphodiesterase
/
SARS-CoV-2
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Cell Biochem Funct
Year:
2023
Document Type:
Article
Affiliation country:
Cbf.3789
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