Can activation of NRF2 be a strategy against COVID-19?

Antonio Cuadrado, Marta Pajares (Lead / Corresponding author), Cristina Benito, José Jiménez-Villegas, Maribel Escoll, Raquel Fernández-Ginés, Angel J. Garcia Yagüe, Diego Lastra, Gina Manda, Ana I. Rojo, Albena T. Dinkova-Kostova (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

143 Citations (Scopus)
122 Downloads (Pure)


Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 is largely the result of a dysregulated host response, followed by damage to alveolar cells and lung fibrosis. Exacerbated proinflammatory cytokines release (cytokine storm) and loss of T lymphocytes (leukopenia) characterize the most aggressive presentation. We propose that a multifaceted anti-inflammatory strategy based on pharmacological activation of nuclear factor erythroid 2 p45-related factor 2 (NRF2) can be deployed against the virus. The strategy provides robust cytoprotection by restoring redox and protein homeostasis, promoting resolution of inflammation, and facilitating repair. NRF2 activators such as sulforaphane and bardoxolone methyl are already in clinical trials. The safety and efficacy information of these modulators in humans, together with their well-documented cytoprotective and anti-inflammatory effects in preclinical models, highlight the potential of this armamentarium for deployment to the battlefield against COVID-19.

Original languageEnglish
Pages (from-to)598-610
Number of pages13
JournalTrends in Pharmacological Sciences
Issue number9
Early online date14 Jul 2020
Publication statusPublished - Sept 2020


  • KEAP1
  • SARS-CoV-2
  • anti-inflammatory ARDS
  • bardoxolone methyl
  • sulforaphane

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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