In a new study, researchers found changes in gene expression suggest possible therapies to prevent and treat COVID-19 based on dexamethasone, calcitriol (vitamin D), and tocopherol (vitamin E).
The therapies may help disrupt the inflammatory “vicious circle” in COVID-19.
The research was conducted by a team at Medical University in Lublin, Poland.
The COVID-19 virus initially has a limited capability to invade, attacking only one intracellular genetic target, the aryl hydrocarbon receptors (AhRs).
Yet it leads to widely diverse clinical symptoms, suggesting multiple pathogenic mechanisms.
In the new study, the team describes how excessive activation of AhRs via the IDO1-kynurenine-AhR signaling pathway, which is used by many pathogens to establish infection, leads to “Systemic AhR Activation Syndrome” (SAAS).
They also hypothesize that therapies targeting the downregulation of AhRs and IDO1 genes should decrease the severity of the infection.
SAAS underlies inflammation, thromboembolism, and fibrosis that may lead to severe disease and death from COVID-19. When coronavirus (CoV) infection persists, it activates IDO1 by massively releasing cytokines.
This in turn perpetuates the already extensive viral activation of AhRs, and the self-limiting control mechanisms of the host immune response may derail, triggering the cytokine storm underlying the most severe symptoms of COVID-19.
The researchers demonstrate that CoVs are perfect viruses leaving nothing to chance and show how difficult it is to stop them after cell invasion.
They describe how many of the features and symptoms of COVID-19 may be dependent on AhR activation, including thromboembolism, fibrosis, multiple organ injury, and brain damage.
They also explore how environmental factors, such as urban dust and diesel fumes, may activate AhRs and make humans more prone to pathogens, including CoV.
The team analyzed major databases to identify chemicals that downregulate both AhR and IDO1, or AhR gene expression.
The molecules they found were dexamethasone for AhR and IDO1, and calcitriol, the active form of vitamin D, which is also known to inhibit the spread of other viral infections, for the AhR gene.
Likewise, tocopherol, a form of Vitamin E, might downregulate IDO1 and is known to play a positive role in response to viral infections and inflammation in aging.
The authors call for more studies and prospective trials to determine if calcitriol and tocopherol supplementation should be recommended for the prevention of COVID-19 infections.
One author of the study is Waldemar A. Turski, MD, PhD from the Department of Experimental and Clinical Pharmacology.
The study is published in Restorative Neurology and Neuroscience.
Copyright © 2020 Knowridge Science Report. All rights reserved.
