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Importantly, the levels of this transcription factor decrease with age. The loss of Nrf2 allows oxidative stress to go unchecked and drives the frailty associated with aging due to disrupted proteostasis, altered genomic stability, increased susceptibility to infection, and cell death.
“It is this age-related frailty that often defines the most vulnerable population in situations such as the one we currently face with the coronavirus pandemic,” writes Joe McCord (Pathways Bioscience, Aurora, USA) and colleagues.
Investigating the effects of Nrf2 activation in human cells
For a virus to be able to replicate, it needs to sustain oxidative stress at a higher level than usual, but not so high as to destroy host cells. Viruses have “learned” to manipulate the Nrf2 pathway in ways that confer survival and enable them to take control from host cells.
Recently, McCord and the team described a potent Nrf2 activator called PB125, which they have now investigated the effects of in human liver-derived HepG2 cells and pulmonary artery endothelial cells.
The team wanted to investigate the changes in gene expression as a result of Nrf2 activation that may be involved in antiviral activity overall, as well as those specifically involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated COVID-19.
https://www.news-medical.net/news/20200518/Potential-new-treatment-approach-to-fatal-COVID-19.aspx
SFX-01 Covid-19 patient trial enrolment expected this month, and backed up as a potential treatment for Covid-19 by recent research from the US. Gla ;-)
16/6/20
SFX-01, has been selected for evaluation in a randomised Phase II/III trial to be sponsored by the University of Dundee ("Dundee"). The trial will investigate whether SFX-01 can reduce the severity, or prevent the onset of, acute respiratory distress syndrome ("ARDS") associated with COVID-19, thus reducing the need for invasive patient ventilation and potentially improving recovery times.
SFX-01 upregulates the Nrf2 pathway which is part of the natural human defence against inflammatory and oxidative stress, such as the inflammation that occurs during a severe viral infection. Preclinical studies have shown that up-regulating the Nrf2 pathway reduces the severity of ARDS, the progressive lung damage observed in COVID-19 patients which can result in the need for invasive ventilation in an intensive care unit.
The trial is being led by Professor James Chalmers, British Lung Foundation Professor of Respiratory Research at the University of Dundee. The study will recruit up to 300 patients with confirmed or suspected COVID-19 from hospitals across the UK. Half the group will receive SFX-01 in addition to standard hospital care while the other half will receive a placebo and standard hospital care. The study is expected to begin enrolment in July, and results are expected in 2021.
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Potential new treatment approach to fatal COVID-19
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May 18 2020
Researchers from the University of Colorado Anschutz Medical Campus and Pathways Bioscience in the United States have found that activating a transcription factor involved in oxidative stress regulation, antiviral activity, and inflammation may serve as a new treatment approach to coronavirus disease 2019 (COVID-19).
The scientists propose that the antiviral and anti-inflammatory effects of activating nuclear factor erythroid 2-related factor 2 (Nrf2) may reduce symptoms and stop the “cytokine storm syndrome” that can be fatal in cases of COVID-19.
A pre-print version of the study can be accessed on the bioRxiv* server, while the manuscript undergoes peer review.
Novel Coronavirus SARS-CoV-2 Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
Novel Coronavirus SARS-CoV-2 Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
The “guardian of healthspan”
As a regulator of cellular redox balance, Nrf2 is often referred to as the “guardian of healthspan,” since it protects against the oxidative stress that can lead to various metabolic and degenerative diseases.