The relevance of selenium to viral disease with special reference to SARS-CoV-2 and COVID-19

Abstract

In this review, the relevance of selenium (Se) to viral disease will be discussed paying particular attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19). Se, the active centre in selenoproteins has an ongoing history of reducing the incidence and severity of viral infections. Host Se deficiency increased the virulence of RNA viruses such as influenza A and coxsackievirus B3, the latter of which is implicated in the development of Keshan disease in north-east China. Significant clinical benefits of Se supplementation have been demonstrated in HIV-1, in liver cancer linked to hepatitis B, and in Chinese patients with hantavirus that was successfully treated with oral sodium selenite. China is of particular interest because it has populations that have both the lowest and the highest Se status in the world. We found a significant association between COVID-19 cure rate and background Se status in Chinese cities; the cure rate continued to rise beyond the Se intake required to optimise selenoproteins, suggesting an additional mechanism. Se status was significantly higher in serum samples from surviving than non-surviving COVID-19 patients. As regards mechanism, SARS-CoV-2 may interfere with the human selenoprotein system; selenoproteins are important in scavenging reactive oxygen species, controlling immunity, reducing inflammation, ferroptosis and endoplasmic reticulum (ER) stress. We found that SARS-CoV-2 significantly suppressed mRNA expression of GPX4, of the ER selenoproteins, SELENOF, SELENOM, SELENOK and SELENOS and down-regulated TXNRD3. Based on the available data, both selenoproteins and redox-active Se species (mimicking ebselen, an inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host) could employ their separate mechanisms to attenuate virus-triggered oxidative stress, excessive inflammatory responses and immune-system dysfunction, thus improving the outcome of SARS-CoV-2 infection.

Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe

“…The analysis of an open-label supplementation study with Zn and Se in patients with severe COVID-19 induced acute respiratory distress syndrome (ARDS) supports the hypothesis of positive health effects on the immune system, but results from sufficiently large and randomized controlled intervention studies are lacking ( 61 ). The understanding of the molecular effects of Se deficiency and supplemental Se intake on the immune system is more solid, as the Se status directly affects the expression of selenoproteins relevant to the immune system ( 62 – 64 ). The link extents to multiple levels, including quality control of newly synthesized proteins in the ER to prevent secretion of immunogenic misfolded proteins ( 65 , 66 ), a direct involvement of selenoproteins in intracellular lymphocyte signaling ( 67 – 69 ), and an effect of selenoproteins, particularly GPX4, on immune cell survival and protection against hyperactivation–induced ferroptosis ( 70 , 71 ).…”

Selenium in Bodily Homeostasis: Hypothalamus, Hormones, and Highways of Communication

“…In addition to its ability to curb oxidative stress, selenium directly regulates thyroid hormone metabolism in the form of the DIO sub-family. Aside from these functions, selenium has been shown to support immunity, bone homeostasis, cardiovascular health, energy metabolism, and various others functions, and has also demonstrated anti-cancer, anti-inflammation, and anti-viral properties, including potentially protecting against SARS-CoV2 infection [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ].…”

Overview of Antiviral Drug Therapy for COVID-19: Where Do We Stand?

“…Phase II clinical trials are ongoing to evaluate the efficacy of ebselen (SPI-1005) in mild and severe COVID-19 patients (NCT04484025/NCT04483973). Ebselen is a synthetic organoselenium with a glutathione peroxidase function which exhibits in vitro antiviral activity against SARS-CoV-2 [ 99 , 100 , 101 ]. Iron level alterations are also detected in COVID-19 patients, related to oxidative stress.…”