Azido-Ceramides, a Tool to Analyse SARS-CoV-2 Replication and Inhibition-SARS-CoV-2 Is Inhibited by Ceramides.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
14 Apr 2023
Historique:
received: 14 03 2023
revised: 12 04 2023
accepted: 12 04 2023
medline: 1 5 2023
pubmed: 28 4 2023
entrez: 28 4 2023
Statut: epublish

Résumé

Recently, we have shown that C6-ceramides efficiently suppress viral replication by trapping the virus in lysosomes. Here, we use antiviral assays to evaluate a synthetic ceramide derivative α-NH2-ω-N3-C6-ceramide (AKS461) and to confirm the biological activity of C6-ceramides inhibiting SARS-CoV-2. Click-labeling with a fluorophore demonstrated that AKS461 accumulates in lysosomes. Previously, it has been shown that suppression of SARS-CoV-2 replication can be cell-type specific. Thus, AKS461 inhibited SARS-CoV-2 replication in Huh-7, Vero, and Calu-3 cells up to 2.5 orders of magnitude. The results were confirmed by CoronaFISH, indicating that AKS461 acts comparable to the unmodified C6-ceramide. Thus, AKS461 serves as a tool to study ceramide-associated cellular and viral pathways, such as SARS-CoV-2 infections, and it helped to identify lysosomes as the central organelle of C6-ceramides to inhibit viral replication.

Identifiants

pubmed: 37108461
pii: ijms24087281
doi: 10.3390/ijms24087281
pmc: PMC10138768
pii:
doi:

Substances chimiques

N-caproylsphingosine 038753E78J
Ceramides 0
Antiviral Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : RTG 2581
Organisme : University of Würzburg
ID : Open Access Publication Fund

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Auteurs

Daniela Brenner (D)

Institute of Organic Chemistry, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany.

Nina Geiger (N)

Institute of Virology and Immunobiology, Julius-Maximilians-Universität Würzburg, 97078 Würzburg, Germany.

Jan Schlegel (J)

Department of Biotechnology and Biophysics, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany.

Viktoria Diesendorf (V)

Institute of Virology and Immunobiology, Julius-Maximilians-Universität Würzburg, 97078 Würzburg, Germany.

Louise Kersting (L)

Institute of Organic Chemistry, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany.

Julian Fink (J)

Institute of Organic Chemistry, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany.

Linda Stelz (L)

Department of Biotechnology and Biophysics, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany.

Sibylle Schneider-Schaulies (S)

Institute of Virology and Immunobiology, Julius-Maximilians-Universität Würzburg, 97078 Würzburg, Germany.

Markus Sauer (M)

Department of Biotechnology and Biophysics, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany.

Jochen Bodem (J)

Institute of Virology and Immunobiology, Julius-Maximilians-Universität Würzburg, 97078 Würzburg, Germany.

Jürgen Seibel (J)

Institute of Organic Chemistry, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany.

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Classifications MeSH