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

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 pro-inflammatory cytokines release (cytokine storm) and loss of T-lymphocytes (leucopenia) characterize the most...

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Detalles Bibliográficos
Autores: Cuadrado, Antonio, Pajares, Marta, Benito, Cristina, Jiménez-Villegas, José, Escoll, Maribel, Fernández-Ginés, Raquel, García-Yagüe, Ángel Juan, Lastra, Diego, Manda, Gina, Rojo, Ana I., Dinkova-Kostova, Albena T.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/216654
Acceso en línea:http://hdl.handle.net/10261/216654
Access Level:acceso abierto
Palabra clave:Anti-inflammatory
ARDS
Bardoxolone methyl
KEAP1
SARS-CoV-2
Sulforaphane
Descripción
Sumario: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 pro-inflammatory cytokines release (cytokine storm) and loss of T-lymphocytes (leucopenia) characterize the most aggressive presentation. Here we propose that a multi-faceted 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 the 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.