tetano
Editor, Senior Moderator
Npj Viruses
. 2024 Feb 21;2(1):6.
doi: 10.1038/s44298-024-00018-4. The Wnt/β-catenin pathway is important for replication of SARS-CoV-2 and other pathogenic RNA viruses
Zaikun Xu[SUP] #[/SUP][SUP] 1 [/SUP], Mohamed Elaish[SUP] #[/SUP][SUP] 1 2 [/SUP], Cheung Pang Wong[SUP] #[/SUP][SUP] 3 [/SUP], Bardes B Hassan[SUP] 4 [/SUP], Joaquin Lopez-Orozco[SUP] 1 [/SUP], Alberto Felix-Lopez[SUP] 3 [/SUP], Natacha S Ogando[SUP] 5 [/SUP], Les Nagata[SUP] 3 [/SUP], Lara K Mahal[SUP] 6 [/SUP], Anil Kumar[SUP] 7 [/SUP], Joyce A Wilson[SUP] 7 [/SUP], Ryan Noyce[SUP] 8 [/SUP], Irv Mayers[SUP] 5 [/SUP], Christopher Power[SUP] 3 5 [/SUP], David Evans[SUP] 3 8 [/SUP], Tom C Hobman[SUP] 9 10 11 [/SUP]
Affiliations
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.
. 2024 Feb 21;2(1):6.
doi: 10.1038/s44298-024-00018-4. The Wnt/β-catenin pathway is important for replication of SARS-CoV-2 and other pathogenic RNA viruses
Zaikun Xu[SUP] #[/SUP][SUP] 1 [/SUP], Mohamed Elaish[SUP] #[/SUP][SUP] 1 2 [/SUP], Cheung Pang Wong[SUP] #[/SUP][SUP] 3 [/SUP], Bardes B Hassan[SUP] 4 [/SUP], Joaquin Lopez-Orozco[SUP] 1 [/SUP], Alberto Felix-Lopez[SUP] 3 [/SUP], Natacha S Ogando[SUP] 5 [/SUP], Les Nagata[SUP] 3 [/SUP], Lara K Mahal[SUP] 6 [/SUP], Anil Kumar[SUP] 7 [/SUP], Joyce A Wilson[SUP] 7 [/SUP], Ryan Noyce[SUP] 8 [/SUP], Irv Mayers[SUP] 5 [/SUP], Christopher Power[SUP] 3 5 [/SUP], David Evans[SUP] 3 8 [/SUP], Tom C Hobman[SUP] 9 10 11 [/SUP]
Affiliations
- PMID: 40295745
- DOI: 10.1038/s44298-024-00018-4
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.