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Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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Related Experiment Video

Updated: Jun 16, 2026

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

Daniela Brenner1, Nina Geiger2, Jan Schlegel3

  • 1Institute of Organic Chemistry, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany.

International Journal of Molecular Sciences
|April 28, 2023
PubMed
Summary

A new synthetic ceramide derivative, AKS461, effectively inhibits SARS-CoV-2 replication by accumulating in lysosomes. This compound confirms the antiviral activity of C6-ceramides, offering a tool for studying viral pathways.

Keywords:
SARS-CoV-2azido-ceramidesceramidessphingolipids

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Area of Science:

  • Virology
  • Cell Biology
  • Drug Discovery

Background:

  • C6-ceramides inhibit viral replication by trapping viruses in lysosomes.
  • SARS-CoV-2 replication can be modulated in a cell-type specific manner.

Purpose of the Study:

  • To evaluate the synthetic ceramide derivative α-NH2-ω-N3-C6-ceramide (AKS461) as an antiviral agent against SARS-CoV-2.
  • To confirm the biological activity of C6-ceramides in inhibiting SARS-CoV-2 replication.
  • To identify the cellular organelle targeted by C6-ceramides for antiviral activity.

Main Methods:

  • Antiviral assays were performed to assess the efficacy of AKS461.
  • Click-labeling with a fluorophore was used to track AKS461 localization within cells.
  • CoronaFISH was employed to confirm viral replication inhibition.

Main Results:

  • AKS461 was shown to accumulate in lysosomes.
  • AKS461 demonstrated significant inhibition of SARS-CoV-2 replication across multiple cell lines (Huh-7, Vero, Calu-3), reducing it by up to 2.5 orders of magnitude.
  • The antiviral activity of AKS461 was comparable to unmodified C6-ceramide.

Conclusions:

  • AKS461 is a potent inhibitor of SARS-CoV-2 replication, acting through lysosomal trapping.
  • Lysosomes are identified as the central organelle for C6-ceramide-mediated antiviral activity.
  • AKS461 serves as a valuable tool for investigating ceramide-related cellular and viral pathways, including SARS-CoV-2 infections.