Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells.
Administration, Inhalation
Ambroxol
/ pharmacology
Animals
Antiviral Agents
/ pharmacology
Biological Transport
Ceramides
/ metabolism
Chlorocebus aethiops
Drug Repositioning
Epithelial Cells
/ drug effects
Expectorants
Gene Expression
Humans
Primary Cell Culture
Reassortant Viruses
/ drug effects
SARS-CoV-2
/ drug effects
Sphingomyelin Phosphodiesterase
/ antagonists & inhibitors
Sphingomyelins
/ metabolism
Spike Glycoprotein, Coronavirus
/ genetics
Vero Cells
Vesiculovirus
/ drug effects
Virus Internalization
/ drug effects
SARS-CoV-2
acid sphingomyelinase
ambroxol
ceramide
human nasal epithelial cells
infection
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
10
01
2021
revised:
15
04
2021
accepted:
21
04
2021
pubmed:
26
4
2021
medline:
14
7
2021
entrez:
25
4
2021
Statut:
ppublish
Résumé
The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, that is, trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol, a mucolytic drug applied by inhalation, suggests that the drug might inhibit the acid sphingomyelinase and thereby infection with SARS-CoV-2. To test this, we used vesicular stomatitis virus pseudoviral particles presenting SARS-CoV-2 spike protein on their surface (pp-VSV-SARS-CoV-2 spike), a bona fide system for mimicking SARS-CoV-2 entry into cells. Viral uptake and formation of ceramide localization were determined by fluorescence microscopy, activity of the acid sphingomyelinase by consumption of [
Identifiants
pubmed: 33895135
pii: S0021-9258(21)00490-7
doi: 10.1016/j.jbc.2021.100701
pmc: PMC8062550
pii:
doi:
Substances chimiques
Antiviral Agents
0
Ceramides
0
Expectorants
0
Sphingomyelins
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Ambroxol
200168S0CL
SMPD1 protein, human
EC 3.1.4.12
Sphingomyelin Phosphodiesterase
EC 3.1.4.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100701Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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