Exploring the therapeutic potential of forkhead box O for outfoxing COVID-19

Open Biol. 2021 Jun;11(6):210069. doi: 10.1098/rsob.210069. Epub 2021 Jun 9.

Abstract

The COVID-19 pandemic has wreaked unprecedented societal havoc worldwide. The infected individuals may present mild to severe symptoms, with nearly 20% of the confirmed patients impaired with significant complications, including multi-organ failure. Acute respiratory distress imposed by SARS-CoV-2 largely results from an aggravated cytokine storm and deregulated immune response. The forkhead box O (FoxO) transcription factors are reported to play a significant role in maintaining normal cell physiology by regulating survival, apoptosis, oxidative stress, development and maturation of T and B lymphocytes, secretion of inflammatory cytokines, etc. We propose a potent anti-inflammatory approach based on activation of the FoxO as an attractive strategy against the novel coronavirus. This regime will be focused on restoring redox and inflammatory homeostasis along with repair of the damaged tissue, activation of lymphocyte effector and memory cells. Repurposing FoxO activators as a means to alleviate the inflammatory burst following SARS-CoV-2 infection can prove immensely valuable in the ongoing pandemic and provide a reliable groundwork for enriching our repertoire of antiviral modalities for any such complication in the future. Altogether, our review highlights the possible efficacy of FoxO activation as a novel arsenal for clinical management of COVID-19.

Keywords: COVID-19; FoxO; coronavirus; cytokines; immune response; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers
  • COVID-19 / epidemiology
  • COVID-19 / metabolism*
  • COVID-19 / virology*
  • COVID-19 Drug Treatment
  • Cytokines / metabolism
  • Disease Management
  • Disease Susceptibility
  • Drug Discovery
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation / drug effects
  • Host-Pathogen Interactions* / genetics
  • Host-Pathogen Interactions* / immunology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Molecular Targeted Therapy
  • Oxidation-Reduction
  • SARS-CoV-2 / physiology*
  • Signal Transduction

Substances

  • Biomarkers
  • Cytokines
  • Forkhead Transcription Factors
  • Inflammation Mediators