Direct pharmacological AMPK activation inhibits mucosal SARS-CoV-2 infection by reducing lipid metabolism, restoring autophagy flux and the type I IFN response.

ABSTRACT: AMP-activated protein kinase (AMPK) plays a central role in regulating cell energy balance. When activated, AMPK suppresses energy-consuming pathways, such as lipid and protein synthesis, while increasing nutrient availability through the activation of autophagy. These pathways downstream of AMPK activation contribute to SARS-CoV-2 infection, which hijacks autophagy and accumulates lipid droplets in viral factories to support viral replication. Here, we assessed the antiviral activity of the direct pan-AMPK allosteric activator MK-8722 in vitro. MK-8722 efficiently inhibited infection of Alpha and Omicron SARS-CoV-2 variants in Vero76 and human bronchial epithelial Calu-3 cells at micromolar concentration. This inhibition relied on restoring the autophagic flux, which redirected new

SUBMITTER: Cottignies-Calamarte A 

PROVIDER: S-EPMC12282067 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature