Targeting 2-Oxoglutarate-Dependent Dioxygenases Promotes Metabolic Reprogramming That Protects against Lethal SARS-CoV-2 Infection in the K18-hACE2 Transgenic Mouse Model.

ABSTRACT: Dysregulation of host metabolism is a feature of lethal SARS-CoV-2 infection. Perturbations in α-ketoglutarate levels can elicit metabolic reprogramming through 2-oxoglutarate-dependent dioxygenases (2-ODDGs), leading to stabilization of the transcription factor HIF-1α. HIF1-α activation has been reported to promote antiviral mechanisms against SARS-CoV-2 through direct regulation of ACE2 expression (a receptor required for viral entry). However, given the numerous pathways HIF-1α serves to regulate it is possible that there are other undefined metabolic mechanisms contributing to the pathogenesis of SARS-CoV-2 independent of ACE2 downregulation. In this study, we used in vitro and in vivo models in which HIF-1α modulation of ACE2 expression was negated, allowing for isolated characterizat

SUBMITTER: Jessop F 

PROVIDER: S-EPMC10587500 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature