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Updated: May 9, 2025

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The Wnt/β-catenin pathway is important for replication of SARS-CoV-2 and other pathogenic RNA viruses

Zaikun Xu1, Mohamed Elaish1,2, Cheung Pang Wong3

  • 1Department of Cell Biology, University of Alberta, Edmonton, AB, Canada.

Npj Viruses
|April 28, 2025
PubMed

Insights

Targeting the Wnt/β-catenin pathway enhances the cellular interferon response against SARS-CoV-2. Inhibiting this pathway boosts peroxisome function, reducing viral replication and COVID-19 symptoms.

Area of Science:

  • Virology
  • Cellular Biology
  • Immunology

Background:

  • The interferon (IFN) response is crucial for controlling viral infections like COVID-19.
  • Peroxisomes, traditionally metabolic organelles, play a role in the IFN response.
  • The Wnt/β-catenin pathway was previously found to suppress peroxisome biogenesis.

Purpose of the Study:

  • To investigate the role of Wnt/β-catenin signaling in SARS-CoV-2 infection.
  • To determine if inhibiting Wnt/β-catenin signaling enhances antiviral defenses.
  • To explore the therapeutic potential of targeting this pathway against viral pathogens.

Main Methods:

  • Assessed SARS-CoV-2-induced Wnt/β-catenin signaling activation.
  • Pharmacologically inhibited the Wnt/β-catenin pathway in infected cells and animal models.
  • Measured peroxisome formation, IFN production, viral replication, and clinical outcomes.

Main Results:

  • SARS-CoV-2 infection activates Wnt/β-catenin signaling.
  • Inhibition of Wnt/β-catenin signaling increased peroxisome biogenesis and IFN production.
  • Wnt/β-catenin inhibition potently reduced SARS-CoV-2 and other RNA virus replication in vitro.
  • Pharmacological targeting decreased viral load, inflammation, and symptoms in a mouse model of COVID-19.

Conclusions:

  • Wnt/β-catenin signaling suppresses antiviral defenses during SARS-CoV-2 infection.
  • Inhibiting Wnt/β-catenin signaling represents a promising therapeutic strategy against SARS-CoV-2 and other viral diseases.
  • Targeting cellular pathways offers potential for broad-spectrum antiviral therapeutics.

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