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Can Activation of NRF2 Be a Strategy against COVID-19?

ABSTRACT: 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.

SUBMITTER: Cuadrado A

PROVIDER: S-EPMC7359808 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Can Activation of NRF2 Be a Strategy against COVID-19?

Cuadrado Antonio A Pajares Marta M Benito Cristina C Jiménez-Villegas José J Escoll Maribel M Fernández-Ginés Raquel R Garcia Yagüe Angel J AJ Lastra Diego D Manda Gina G Rojo Ana I AI Dinkova-Kostova Albena T AT

Trends in pharmacological sciences 20200714 9

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 ...[more]

PMID: 32711925

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Project description:ObjectivesTo investigate the impact of targeted vaccination strategies on morbidity and mortality due to COVID-19, as well as on the incidence of SARS-CoV-2, in India.DesignMathematical modelling.SettingsIndian epidemic of COVID-19 and vulnerable population.Data sourcesCountry-specific and age-segregated pattern of social contact, case fatality rate and demographic data obtained from peer-reviewed literature and public domain.ModelAn age-structured dynamical model describing SARS-CoV-2 transmission in India incorporating uncertainty in natural history parameters was constructed.InterventionsComparison of different vaccine strategies by targeting priority groups such as keyworkers including healthcare professionals, individuals with comorbidities (24-60 years old) and all above 60.Main outcome measuresIncidence reduction and averted deaths in different scenarios, assuming that the current restrictions are fully lifted as vaccination is implemented.ResultsThe priority groups together account for about 18% of India's population. An infection-preventing vaccine with 60% efficacy covering all these groups would reduce peak symptomatic incidence by 20.6% (95% uncertainty intervals (UI) 16.7-25.4) and cumulative mortality by 29.7% (95% CrI 25.8-33.8). A similar vaccine with ability to prevent symptoms (but not infection) will reduce peak incidence of symptomatic cases by 10.4% (95% CrI 8.4-13.0) and cumulative mortality by 32.9% (95% CrI 28.6-37.3). In the event of insufficient vaccine supply to cover all priority groups, model projections suggest that after keyworkers, vaccine strategy should prioritise all who are >60 and subsequently individuals with comorbidities. In settings with weakest transmission, such as sparsely populated rural areas, those with comorbidities should be prioritised after keyworkers.ConclusionsAn appropriately targeted vaccination strategy would witness substantial mitigation of impact of COVID-19 in a country like India with wide heterogeneity. 'Smart vaccination', based on public health considerations, rather than mass vaccination, appears prudent.

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Can Activation of NRF2 Be a Strategy against COVID-19?

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Can Activation of NRF2 Be a Strategy against COVID-19?

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