Reactive oxygen species are associated with the inhibitory effect of N-(4-hydroxyphenyl)-retinamide on the entry of the severe acute respiratory syndrome-coronavirus 2.
J Biochem
; 173(5): 337-342, 2023 Apr 26.
Artículo
en Inglés
| MEDLINE | ID: covidwho-2262469
ABSTRACT
N-(4-hydroxyphenyl)-retinamide (4-HPR) inhibits the dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity. We previously reported that 4-HPR suppresses the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spike protein-mediated membrane fusion through a decrease in membrane fluidity in a DEGS1-independent manner. However, the precise mechanism underlying the inhibition of viral entry by 4-HPR remains unclear. In this study, we examined the role of reactive oxygen species (ROS) in the inhibition of membrane fusion by 4-HPR because 4-HPR is a well-known ROS-inducing agent. Intracellular ROS generation was found to be increased in the target cells in a cell-cell fusion assay after 4-HPR treatment, which was attenuated by the addition of the antioxidant, α-tocopherol (TCP). The reduction in membrane fusion susceptibility by 4-HPR treatment in the cell-cell fusion assay was alleviated by TCP addition. Furthermore, fluorescence recovery after photobleaching analysis showed that the lateral diffusion of glycosylphosphatidylinositol-anchored protein and SARS CoV-2 receptor was reduced by 4-HPR treatment and restored by TCP addition. These results indicate that the decrease in SARS-CoV-2 spike protein-mediated membrane fusion and membrane fluidity by 4-HPR was due to ROS generation. Taken together, these results demonstrate that ROS production is associated with the 4-HPR inhibitory effect on SARS-CoV-2 entry.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Fenretinida
/
COVID-19
/
Antineoplásicos
Tipo de estudio:
Estudio experimental
Límite:
Humanos
Idioma:
Inglés
Revista:
J Biochem
Año:
2023
Tipo del documento:
Artículo
País de afiliación:
Jb
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