Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

Abstract

Infection with SARS-CoV-2 causes the coronavirus infectious disease 2019 (COVID-19), a pandemic that has, at present, infected more than 11 million people globally. Some COVID-19 patients develop a severe and critical illness, spurred on by excessive inflammation that can lead to respiratory or multiorgan failure. Numerous studies have established the unique array of cytoprotective properties of the dietary amino acid ergothioneine. Based on studies in a range of in vitro and in vivo models, ergothioneine has exhibited the ability to modulate inflammation, scavenge free radicals, protect against acute respiratory distress syndrome, prevent endothelial dysfunction, protect against ischemia and reperfusion injury, protect against neuronal damage, counteract iron dysregulation, hinder lung and liver fibrosis, and mitigate damage to the lungs, kidneys, liver, gastrointestinal tract, and testis, amongst many others. When compiled, this evidence suggests that ergothioneine has a potential application in the treatment of the underlying pathology of COVID-19. We propose that ergothioneine could be used as a therapeutic to reduce the severity and mortality of COVID-19, especially in the elderly and those with underlying health conditions. This review presents evidence to support that proposal.

Keywords: COVID-19; NETs; SARS; antioxidant; coronavirus; cytokine; ergothioneine; inflammation.

Figure 1

Summary of possible mechanisms of action of ET: (A) An overview of the possible direct and indirect mechanisms by which ET can reduce the severity of symptoms in COVID-19 patients and thereby reduce mortality [33,34,35,36,37,38,39,40,41,43,45,46,47,48,50,51,52,53,55,56,57,58,61,62,63,68,96,97,98,99,100,104,119,131,132,133,152,153,184,185,186,203]. (B) Population studies have shown that lower blood levels of ET are associated with a wide range of disorders and frailty, suggesting that supplementation may assist or reduce the risk of these conditions. These disorders are also comorbidities that likely increase the risk of mortality due to COVID-19, possibly highlighting the greater therapeutic value of ET for these individuals [60,64,72,74,75,105]. (C) Conversely, silencing the ET transporter in animal studies increases susceptibility to diseases and may elevate oxidative damage and inflammation in these models [101,102,103,105].

Figure 2

Summary of tissue protection by ET [24,32,38,45,46,47,48,51,52,53,54,55,56,57,58,59,60,62,63,64,68,74,98,101,104,105,131,183,184,185,186,187,188,189,190,227,228,236,242]. There is evidence to suggest that ET can accumulate in most (if not all tissues) in the body, especially those shown below. Based on present knowledge, the following diagram highlights how ET may protect various organs and tissues from oxidative damage and inflammatory injury amongst other cytoprotective effects in COVID-19 patients. The boxes in blue highlight systemic benefits for all tissues of the body [33,34,35,36,37,38,39,43,45,48,50,65,66,67,68,96,97,98,99,100,101,154].