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

Daniela BrennerNina GeigerJan SchlegelViktoria DiesendorfLouise KerstingJulian FinkLinda StelzSibylle Schneider-SchauliesMarkus SauerJochen BodemJuergen Seibel
Published in: International journal of molecular sciences (2023)
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.
Keyphrases
  • sars cov
  • respiratory syndrome coronavirus
  • induced apoptosis
  • high throughput
  • cell proliferation
  • room temperature
  • endoplasmic reticulum stress
  • cell cycle arrest