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Published 21 February 2024
DOI https://doi.org/10.1038/s44298-024-00018-4
Xu, Z., Elaish, M., Wong, C.P. et al.
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.
DOI https://doi.org/10.1038/s44298-024-00018-4
Xu, Z., Elaish, M., Wong, C.P. et al.
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.
