Selenium and RNA Virus Interactions: Potential Implications for SARS-CoV-2 Infection (COVID-19)

Abstract

SARS-CoV-2 is an RNA virus responsible for the COVID-19 pandemic that already claimed more than 340,000 lives worldwide as of May 23, 2020, the majority of which are elderly. Selenium (Se), a natural trace element, has a key and complex role in the immune system. It is well-documented that Se deficiency is associated with higher susceptibility to RNA viral infections and more severe disease outcome. In this article, we firstly present evidence on how Se deficiency promotes mutations, replication and virulence of RNA viruses. Next, we review how Se might be beneficial via restoration of host antioxidant capacity, reduction of apoptosis and endothelial cell damages as well as platelet aggregation. It also appears that low Se status is a common finding in conditions considered at risk of severe COVID-19, especially in the elderly. Finally, we present a rationale for Se use at different stages of COVID-19. Se has been overlooked but may have a significant place in COVID-19 spectrum management, particularly in vulnerable elderly, and might represent a game changer in the global response to COVID-19.

Understanding selenium and glutathione as antiviral factors in COVID-19: Does the viral Mpro protease target host selenoproteins and glutathione synthesis?

“…Several independent studies have now established a significant association between the outcome of COVID-19 and previously documented regional selenium (Se) status in Chinese cities (1), and a similar relationship between serum Se and mortality in a European cohort of COVID-19 patients (2). These observations invite questions about the mechanisms involved, particularly because they fit into a consistent pattern of a role for Se that has been reported over several decades for a variety of RNA viruses (enteroviruses, hantaviruses, and influenza A) and viruses with an RNA stage (HIV-1 and Hepatitis B virus), as reviewed by various authors (3)(4)(5).…”

Selenium (Se) plays a key role in the biological effects of some viruses: Implications for COVID-19

“…This condition will also lead to the decrease of host TrxR, thus affecting the antioxidant capacity of host cells ( Guillin et al, 2019 ). Supplementation of selenite can restore the biosynthesis of TrxR in host cells, thereby rebuilding the DNA-synthesis and antioxidant capacities of cells ( Hiffler et al, 2020 ; Kieliszek et al, 2020 ).…”

“…Although both viruses typically cause mild, self-limiting symptoms such as fever, rash, and upper respiratory illness, severe CVB infections can cause more life-threatening and endemic diseases like Keshan disease, which occurs in a well-known area with Se deficiency in China ( Fang et al, 2015 ). The degree of myocardial injury in patients with Keshan disease is correlated with oxidative stress, and selenoenzymes are also considered to be involved in its pathogenesis ( Pei et al, 2013 ; Hiffler et al, 2020 ). Severe oxidative stress responses were found in patients with COVID-19 ( Manzanares et al, 2021 ).…”

“…Similarly, clinical trials have also demonstrated the positive effect of Se on influenza immune response. Patients with influenza (H1N1) pneumonia had greater Se deficiency than the control group, and patients with H1N1 whose blood Se levels were best for GPx activity recovered more easily and had a higher survival rate than patients with low Se levels ( Hiffler et al, 2020 ). Based on the above response between Se and influenza virus, nanomaterials containing Se have been developed to fight H1N1 virus, and these drugs have shown positive effects in inhibiting virus-induced apoptosis and preventing viral infection in Madin–Darby Canine Kidney cells ( Li et al, 2018 ; Wang et al, 2020 ).…”

“…Se is an important and essential trace element in mammalian redox biology ( Zhang et al, 2020a ), and its positive effects on viral diseases (including Ebola and hantavirus disease) have been reported in both experimental and clinical applications ( Fang et al, 2015 ; Eimoemen et al, 2016 ; Guillin et al, 2019 ). Dietary Se deficiency can affect host immunity and alter virus virulence ( Hiffler et al, 2020 ). Hence, we hypothesized that the incidence of COVID-19 in Hubei might be related to Se levels in the local environment.…”