"1. Introduction
Lung inflammation is the main cause of life-threatening respiratory disorders at the severe stage of SARS-CoV-2 infection, characterized by the so-called 'cytokine release syndrome (CRS)'.
The key to fighting this harmful inflammatory response resides in: (i) addressing the mechanism of the virus penetration into the cell, mediated by binding to and inactivation of the ACE2 protein; (ii) contrasting the exacerbation of the inflammatory response...
2. Cellular GSH Homeostasis
Glutathione, a tripeptide composed of glutamate, cysteine and glycine, is an antioxidant molecule ubiquitous in most living organisms...
Due to the strong cytoprotective effects of GSH, alterations in GSH homeostasis have been associated with neurodegenerative diseases, AIDS, liver and heart disease, aging, diabetes mellitus and cancer...
3. The Protective Actions of GSH
Glutathione can prevent damage to important cellular components caused by ROS [reactive oxygen species] and their derivatives, such as free radicals, peroxides, lipid peroxides, or by organic pollutants and heavy metals... Among the many functions of GSH, some are worthy of mention in relation to their impact on the exacerbated inflammation taking place in COVID-19 and in relation to the symptoms developed in the disease...
As a consequence of the competition between these and many other GSH-consuming pathways, on one hand, the raging inflammation and oxidative stress triggered by the viral infection steals GSH from core functions such as NO-dependent vasodilatation; on the other hand, when other biochemical pathways are consuming GSH, the patient is not protected from an inflammation that can prove fatal.
7. Conclusions
... Several pieces of evidence reported in our biochemical analysis suggest that low levels of GSH could be one of the major causes of the excessive inflammatory response linked to severe COVID-19 symptoms and indicate that increasing body GSH could reduce the number of symptomatic patients."
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