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.
Artículo
en Inglés
| 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.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Esfingomielina Fosfodiesterasa
/
SARS-CoV-2
/
COVID-19
Límite:
Humanos
Idioma:
Inglés
Revista:
Cell Biochem Funct
Año:
2023
Tipo del documento:
Artículo
País de afiliación:
Cbf.3789
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