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

  • Npj Viruses. 2024 Feb 21;2(1):6. doi: 10.1038/s44298-024-00018-4.
Zaikun Xu  #  1 ,  Mohamed Elaish  #  1  2 ,  Cheung Pang Wong  #  3 ,  Bardes B Hassan  4 ,  Joaquin Lopez-Orozco  1 ,  Alberto Felix-Lopez  3 ,  Natacha S Ogando  5 ,  Les Nagata  3 ,  Lara K Mahal  6 ,  Anil Kumar  7 ,  Joyce A Wilson  7 ,  Ryan Noyce  8 ,  Irv Mayers  5 ,  Christopher Power  3  5 ,  David Evans  3  8 ,  Tom C Hobman  9  10  11
Affiliations
  • 1. Department of Cell Biology, University of Alberta, Edmonton, AB, Canada.
  • 2. Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
  • 3. Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, Canada.
  • 4. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
  • 5. Department of Medicine, University of Alberta, Edmonton, AB, Canada.
  • 6. Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
  • 7. Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.
  • 8. Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.
  • 9. Department of Cell Biology, University of Alberta, Edmonton, AB, Canada. [email protected].
  • 10. Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, Canada. [email protected].
  • 11. Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada. [email protected].
  • # Contributed equally.
PMID: 40295745 DOI: 10.1038/s44298-024-00018-4
Abstract

Understanding how viruses affect cellular pathways during Infection may facilitate development of host cell-targeted therapeutics with broad-spectrum Antiviral activity. The interferon (IFN) response is critical for reducing replication and pathogenesis of many viruses including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. Mounting evidence indicates that peroxisomes which are best known as metabolic organelles, function in the IFN response. Recently, we reported that the Wnt/β-catenin signaling pathway strongly suppresses peroxisome biogenesis. Here, we show that SARS-CoV-2 Infection activates Wnt/β-catenin signaling and hypothesized that pharmacological inhibition of this pathway would result in increased peroxisome formation and enhanced IFN production. Indeed, Wnt/β-catenin signaling potently inhibits replication of SARS-CoV-2 and Other pathogenic RNA viruses in vitro and reduces viral load, inflammation and clinical symptoms in a mouse model of COVID-19. As such, targeting this cellular pathway may have prophylactic and/or therapeutic value in reducing the disease burden caused by emerging viral pathogens.

Products