Nrf2 Activator PB125 as a Potential Therapeutic Agent Against COVID-19
Joe M McCord, Brooks M. Hybertson, Adela Cota-Gomez, Bifeng Gao
doi: https://doi.org/10.1101/2020.05.16.099788
Abstract
Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2 activating composition PB125 down regulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-Cov-2 entry into host cells. Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells we report the marked down regulation by PB125 of 36 genes encoding cytokines. These include IL1-beta, IL6, TNF-alpha the cell adhesion molecules ICAM1, VCAM1, and E-selectin, and a group of IFN-gamma-induced genes.
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