The possible role of nuclear factor erythroid-2-related factor 2 activators in the management of Covid-19

J Biochem Mol Toxicol. 2024 Jan;38(1):e23605. doi: 10.1002/jbt.23605. Epub 2023 Dec 9.

Abstract

COVID-19 is caused by a novel SARS-CoV-2 leading to pulmonary and extra-pulmonary manifestations due to oxidative stress (OS) development and hyperinflammation. COVID-19 is primarily asymptomatic though it may cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), systemic inflammation, and thrombotic events in severe cases. SARS-CoV-2-induced OS triggers the activation of different signaling pathways, which counterbalances this complication. One of these pathways is nuclear factor erythroid 2-related factor 2 (Nrf2), which induces a series of cellular interactions to mitigate SARS-CoV-2-mediated viral toxicity and OS-induced cellular injury. Nrf2 pathway inhibits the expression of pro-inflammatory cytokines and the development of cytokine storm in COVID-19. Therefore, Nrf2 activators may play an essential role in reducing SARS-CoV-2 infection-induced inflammation by suppressing NLRP3 inflammasome in COVID-19. Furthermore, Nrf2 activators can attenuate endothelial dysfunction (ED), renin-angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Thus this mini-review tries to clarify the possible role of the Nrf2 activators in the management of COVID-19. Nrf2 activators could be an effective therapeutic strategy in the management of Covid-19. Preclinical and clinical studies are recommended in this regard.

Keywords: Covid-19; SARS CoV-2; angiotensin-converting enzyme; nuclear factor erythroid 2-related factor 2; oxidative stress.

Publication types

  • Review

MeSH terms

  • COVID-19*
  • Humans
  • Inflammation
  • Lung
  • NF-E2-Related Factor 2
  • SARS-CoV-2

Substances

  • NF-E2-Related Factor 2