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Correlation between COVID-19 cure rate in 17 cities outside Hubei on Feb 18, 2020, and city population selenium status (hair selenium concentration) analysed using weighted linear regression. Each data point represents the cure rate, calculated as percentage of patients hospitalized with SARS-CoV-2 deemed to be cured*. The size of the marker is proportional to the number of cases (adapted from Am J Clin Nutr [7] with permission). From the graph of Se intake vs hair Se concentration, Supplemental Figure 1, Seintake = 232.98 Sehair – 44.521,allowing the calculation of corresponding values of selenium intake and hair concentration (Supplemental Table 3). Thus value A represents the hair concentration corresponding to an intake of 55 μg/d where platelet GPX1 activity is maximised [58], value B represents the hair concentration corresponding to an intake of 105 μg/d where SELENOP concentration is maximised [58], and value C is the hair selenium concentration (1.0 mg/kg) at the maximum cure rate in the investigated cities which corresponds to an intake of 188 μg/d.*Cured patients are those in whom temperature has returned to normal for more than 3 days, respiratory symptoms are significantly improved, lung imaging shows significant reduction of inflammation, negative nucleic acid test of respiratory pathogen on two consecutive occasions with a sampling interval of at least 1 day.

Correlation between COVID-19 cure rate in 17 cities outside Hubei on Feb 18, 2020, and city population selenium status (hair selenium concentration) analysed using weighted linear regression. Each data point represents the cure rate, calculated as percentage of patients hospitalized with SARS-CoV-2 deemed to be cured*. The size of the marker is proportional to the number of cases (adapted from Am J Clin Nutr [7] with permission). From the graph of Se intake vs hair Se concentration, Supplemental Figure 1, Seintake = 232.98 Sehair – 44.521,allowing the calculation of corresponding values of selenium intake and hair concentration (Supplemental Table 3). Thus value A represents the hair concentration corresponding to an intake of 55 μg/d where platelet GPX1 activity is maximised [58], value B represents the hair concentration corresponding to an intake of 105 μg/d where SELENOP concentration is maximised [58], and value C is the hair selenium concentration (1.0 mg/kg) at the maximum cure rate in the investigated cities which corresponds to an intake of 188 μg/d.*Cured patients are those in whom temperature has returned to normal for more than 3 days, respiratory symptoms are significantly improved, lung imaging shows significant reduction of inflammation, negative nucleic acid test of respiratory pathogen on two consecutive occasions with a sampling interval of at least 1 day.

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Selenium is a trace element essential to human health largely because of its incorporation into selenoproteins that have a wide range of protective functions. Selenium has an ongoing history of reducing the incidence and severity of various viral infections; for example, a German study found selenium status to be significantly higher in serum sampl...

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... 115,117 Infection of Vero E6 cells with SARS-CoV-2 markedly down-regulated the expression of a number of selenoproteins, at the same time triggering the expression of IL-6 inflammatory cytokine. 101,118 SARS-CoV-2 interferes with the host's selenoprotein system, and it is thought that a deficient status might occur during the acute phase of disease under conditions of enhanced viral replication. It has been suggested that redox-active selenium species resulted from high selenium intake are likely to lead to SARS-CoV-2 protease inhibition. ...
... It has been suggested that redox-active selenium species resulted from high selenium intake are likely to lead to SARS-CoV-2 protease inhibition. 101,119 Ebselen is an organoselenium compound endowed with antiviral potential, consisting in inhibition of main SARS-CoV-2 protease and acts as glutathione peroxidase and peroxiredoxin mimetic. 91,120 The ebselen-induced inhibition of SARS-CoV-2 protease relies on the selenosulfide formed from reaction between ebselen and protein thiols. ...
... 91,120 The ebselen-induced inhibition of SARS-CoV-2 protease relies on the selenosulfide formed from reaction between ebselen and protein thiols. 101,121 This inhibitory action of ebselen was assigned to its interaction with Cys145 and His41 residues present in the active site of main protease. 122,123 Sodium selenite, another seleniumcontaining compound endowed with antiviral potential, oxidizes −SH groups in the viral disulfide isomerase, imparting viral inaccessibility to healthy cells. ...
Article
Viral pathologies encompass activation of pro-oxidative pathways and inflammatory burst. Alleviating overproduction of reactive oxygen species and cytokine storm in COVID-19 is essential to counteract the immunogenic damage in endothelium and alveolar membranes. Antioxidants alleviate oxidative stress, cytokine storm, hyperinflammation, and diminish the risk of organ failure. Direct antiviral roles imply: impact on viral spike protein, interference with the ACE2 receptor, inhibition of dipeptidyl peptidase 4, transmembrane protease serine 2 or furin, and impact on of helicase, papain-like protease, 3-chyomotrypsin like protease, and RNA-dependent RNA polymerase. Prooxidative environment favors conformational changes in the receptor binding domain, promoting the affinity of the spike protein for the host receptor. Viral pathologies imply a vicious cycle, oxidative stress promoting inflammatory responses, and vice versa. The same was noticed with respect to the relationship antioxidant impairment-viral replication. Timing, dosage, pro-oxidative activities, mutual influences, and interference with other antioxidants should be carefully regarded. Deficiency is linked to illness severity.
... The antiviral and antibacterial activity of the lactoperoxidase system has shown substrate-specific outcomes with possibly the best effects in case of iodide and selenium [84,95]. In line with this, selenium status above that required for optimal selenoprotein function has been associated with better cure rate from COVID-19 [96]. In addition, selenium deficiency is associated with increased virulence of certain viruses through accelerated mutation [97,98], which is probably the main pathophysiological basis of Keshan disease [38,98]. ...
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Iodide is an antioxidant, oxidant and thyroid hormone constituent. Selenoproteins are needed for triiodothyronine synthesis, its deactivation and iodine release. They also protect thyroidal and extrathyroidal tissues from hydrogen peroxide used in the ‘peroxidase partner system’. This system produces thyroid hormone and reactive iodine in exocrine glands to kill microbes. Exocrine glands recycle iodine and with high urinary clearance require constant dietary supply, unlike the thyroid. Disbalanced iodine-selenium explains relations between thyroid autoimmune disease (TAD) and cancer of thyroid and exocrine organs, notably stomach, breast, and prostate. Seafood is iodine unconstrained, but selenium constrained. Terrestrial food contains little iodine while selenium ranges from highly deficient to highly toxic. Iodine vs. TAD is U-shaped, but only low selenium relates to TAD. Oxidative stress from low selenium, and infection from disbalanced iodine-selenium, may generate cancer of thyroid and exocrine glands. Traditional Japanese diet resembles our ancient seashore-based diet and relates to aforementioned diseases. Adequate iodine might be in the milligram range but is toxic at low selenium. Optimal selenoprotein-P at 105 µg selenium/day agrees with Japanese intakes. Selenium upper limit may remain at 300–400 µg/day. Seafood combines iodine, selenium and other critical nutrients. It brings us back to the seashore diet that made us what we currently still are.
... Some organoselenium compounds affect mood and exhibit high antidepressant activity [11,12]. They possess powerful radical scavenging and broad anti-HIV activity [13] and are capable of blocking the replication of SARS-CoV-2 [14][15][16]. One of the actively studied properties of organoselenium compounds is their glutathione peroxidase activity, [17,18] protecting living organisms against oxidative stress. ...
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A one-pot synthesis of linear and cyclic β-alkoxyselenides is developed through the iodine-mediated three-component reaction of elemental selenium with alkenes (dienes) and alcohols. Selenylation of 1,5-hexadiene gives 2,5-di(methoxymethyl)tetrahydroselenophene and 2-methoxy-6-(methoxymethyl)tetrahydro-2H-selenopyran via the 5-exo-trig and 6-endo-trig cyclization. 1,7-Octadiene affords only linear 1:2 adduct with two terminal double bonds. 1,5-Cyclooctadiene results in one diastereomer of 2,6-dialkoxy-9-selenabicyclo [3.3.1]nonanes via 6-exo-trig cyclization. With 1,3-diethenyl-1,1,3,3-tetramethyldisiloxane, the first ring-substituted representative of a very rare class of heterocycles, 1,4,2,6-oxaselenadisilinanes, was obtained at a high yield.
... This is mainly related to its incorporation into selenocysteine (SeCys), which is a pivotal component of the selenoproteins. These are involved in the maintenance of the redox homeostasis, regulation of the inflammatory cascade, and the modulation of the immune response [135,[147][148][149][150]. Furthermore, it should be emphasized that oxidative stress is one of the main features of viral infections (especially respiratory ones) [134][135][136]147]. ...
... Over the last three years, several studies focusing on the relationship between Se and SARS-CoV-2 have been reported [5,24,42,64,136,137,[147][148][149]171]. There is a growing body of evidence that the cysteine 145 residues of SARS-CoV-2 M membrane glycoprotein plays a key role in the replication of this virus [5,137,148]. ...
... Over the last three years, several studies focusing on the relationship between Se and SARS-CoV-2 have been reported [5,24,42,64,136,137,[147][148][149]171]. There is a growing body of evidence that the cysteine 145 residues of SARS-CoV-2 M membrane glycoprotein plays a key role in the replication of this virus [5,137,148]. For this reason, it is considered an excellent target for reducing the replication, transcription, and truncating of the life cycle of the SARS-CoV-2 virus. ...
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Selenium (Se) is an essential element for human health as it is involved in different physiological functions. Moreover, a great number of Se compounds can be considered potential agents in the prevention and treatment of some diseases. It is widely recognized that Se activity is related to multiple factors, such as its chemical form, dose, and its metabolism. The understanding of its complex biochemistry is necessary as it has been demonstrated that the metabolites of the Se molecules used to be the ones that exert the biological activity. Therefore, the aim of this review is to summarize the recent information about its most remarkable metabolites of acknowledged biological effects: hydrogen selenide (HSe−/H2Se) and methylselenol (CH3SeH). In addition, special attention is paid to the main seleno-containing precursors of these derivatives and their role in different pathologies.
... A number of selenoproteins (Table 1) are directly or indirectly involved in combatting viral infections through functions relating to antioxidant defence, redox signalling and redox homoeostasis (9) . A balance exists between the generation of ROS and their scavenging systems, and this equilibrium can be disturbed during viral infections, resulting in oxidative stress. ...
... In the early 1930s an endemic cardiomyopathy termed Keshan disease (3) was described in Heilongjiang province, Northeast China, where severe selenium deficiency is Table 1. Examples of selenoproteins involved in viral infections (9) General function Selenoproteins Antioxidant/redox function GPX1, GPX2, GPX3, GPX4, TXNRD1, TXNRD2, TXNRD3, MSRB1, SELENOP, SELENOW Anti-inflammatory GPX, TXNRD1, SELENOS Immune cell function GPX, TXNRD, MSRB1, SELENOK, SELENOS Anti-viral effects GPX, TXNRD, ER selenoproteins GPX1, cytosolic glutathione peroxidase; GPX2, gastrointestinal glutathione peroxidase; GPX3, extracellular glutathione peroxidase; GPX4, phospholipid glutathione peroxidase; TXNRD1, cytosolic thioredoxin reductase; TXNRD2, mitochondrial (2) 70/70 IOM 2000 (33) 45/45 55/55 WHO 2004 (34) 27/20* 34/26 UK 1991 (35) 75/60 { D-A-CH 2015 (16) 70/60 NNR 2012 (36) 35/30 60/50 AESAN 2019 (37) 70/55 ANSES 2021 (38) 70/70 SINU 2014 (39) 55/55 HCNL 2018 (40) 70/70 NRVANZ 2006 (41) 60/50 70/60 CNS 2013 (42) 50/50 60/60 JAPAN 2020 (43) 25/20 30/25 AR, average requirement (intake that meets the needs of 50% of the population); EAR, estimated average requirement (intake that meets the needs of 50% of the population); PRI, population reference intake (intake that meets the needs of 97⋅5% of the population); RDA, RDA (intake that meets the needs of 97⋅5% of the population); RNI, reference nutrient intake (intake that meets the needs of 97⋅5% of the population); AI, adequate intake (intake that meets or exceeds the needs of 100% (34) . { Lower reference nutrient intake (LRNI), the intake below which the needs of 97⋅5% of adult men and women are not met, is 40 μg/d. ...
Article
Selenium is found at the active centre of twenty-five selenoproteins which have a variety of roles, including the well-characterised function of antioxidant defense, but it also is claimed to be involved in the immune system. However, due to limited and conflicting data for different parameters of immune function, intakes of selenium that have an influence on immune function are uncertain. This review covers the relationship between selenium and immune function in man, focusing on the highest level of evidence, namely that generated by randomised controlled trials (RCT), in which the effect of selective administration of selenium, in foods or a supplement, on immune function was assessed. A total of nine RCT were identified from a systematic search of the literature, and some of these trials reported effects on T and natural killer cells, which were dependent on the dose and form of selenium administered, but little effect of selenium on humoral immunity. There is clearly a need to undertake dose–response analysis of cellular immunity data in order to derive quantitative relationships between selenium intake and measures of immune function. Overall, limited effects on immunity emerged from experimental studies in human subjects, though additional investigation on the potential influence of selenium status on cellular immunity appears to be warranted.
... Selenium deficiency is very prevalent in severely extremely sick individuals [49,50]. Low selenium status is also more common among patients with COVID-19 with severe illness [47,51]. Supplementation with selenium improves immunological function and reduces oxidative stress, inflammation, and virus pathogenicity [52][53][54]. ...
... Supplementation with selenium improves immunological function and reduces oxidative stress, inflammation, and virus pathogenicity [52][53][54]. Supplementation with selenium and selenium-containing compounds may also reduce the capacity of SARS-CoV-2 to infect humans [51]. Selenium supplementation has been found to improve the immunological functions of elderly individuals. ...
Article
Background Coronavirus disease 2019 (COVID-19) is a systemic disease affecting multiple organs. Furthermore, viral infection depletes several trace elements and promotes complex biochemical reactions in the body. Smoking has been linked to the incidence of COVID-19 and associated mortality, and it may impact clinical effects, viral and bacterial conversion, and treatment outcomes. Objectives To study the relationship between severe acute respiratory syndrome coronavirus type 2 and the elemental concentrations of selenium (Se) and mercury (Hg) in biological samples from smokers and nonsmokers infected with the virus and in healthy individuals. Method We evaluated changes in the concentrations of essential (Se) and toxic (Hg) elements in biological samples (blood, nasal fluid, saliva, sputum, serum, and scalp hair) collected from male smokers and nonsmokers (aged 29–59 years) infected with COVID-19 and from healthy men in the same age group. The patients lived in different cities in Sindh Province, Pakistan. The Se and Hg concentrations were determined using atomic absorption spectrophotometry. Results Se concentrations in all types of biological samples from smokers and nonsmokers with COVID-19 were lower than those of healthy smokers and nonsmokers. Hg concentrations were elevated in both smokers and nonsmokers with COVID-19. Conclusions In the current study, persons infected with COVID-19 had higher concentrations of toxic Hg, which could cause physiological disorders, and low concentrations of essential Se, which can also cause weakness. COVID-19 infection showed positive correlations with levels of mercury and selenium. Thus, additional clinical and experimental investigations are essential.
... In human immunodeficiency virus patients, the decreases in survival rate with the decline in selenium level have been known, and the significance of the selenium levels against several infectious diseases, such as influenza virus, hepatitis virus, and West Nile virus, has been shown (Verma et al. 2008, Himoto et al. 2011, Yu et al. 2011, Rayman 2012. Furthermore, the relevance of the coronavirus disease 2019 (COVID-19) has been actively investigated, and the correlation between selenium levels and the risk of aggravation or the cure rate in the infection of SARS-CoV-2 has been reported (Zhang et al. 2020). ...
Article
The essential trace element selenium plays a significant role in redox homeostasis in the human body. Selenium is very reactive and has a potent toxicity; however, the living body cleverly utilizes its reactivity for redox reactions. The biological function of selenium is mainly mediated by selenoproteins, which contain selenocysteine, a cysteine analogue that possesses selenium instead of sulphur. Twenty-five types of human selenoproteins have been identified, including glutathione peroxidase (GPX; for the reduction of hydrogen peroxide and lipid hydroperoxide) and thioredoxin reductase (for redox regulation). Selenoprotein P (SELENOP), which is a major selenoprotein in the plasma, is mainly synthesized in the liver and secreted into the plasma. As a multifunctional protein with selenium-transport activity, GPX-like activity and metal-binding properties, SELENOP plays a vital role in selenium metabolism and redox regulation. This review focuses on the relationship between selenium metabolism and redox regulation, particularly the physiological role of selenoproteins and the pathophysiological implications of its disorder. Furthermore, the significant roles of selenium in infectious diseases and its utility for phylaxis are discussed.
... Selenium is an essential trace element for mammalian redox balance, and the human genome contains at least 25 genes that encode selenoproteins. Selenocysteine is localized in the catalytic centers of many selenoproteins that counteract SARS-CoV-2 infection (Fairweather-Tait et al., 2011;J. Zhang et al., 2020a). Thus, an association between the rate of recovery of SARS-CoV-2-infected patients and Se status has been reported in humans receiving adequate or insufficient Se (J. Zhang et al., 2020b). Moghaddam et al. showed that Se concentrations were significantly higher in surviving COVID-19 cases compared to the non-survivors. The Se levels wer ...
... This should be noted as an important therapeutic target (J. Zhang et al., 2020a). ...
Article
In severe COVID-19, the levels of iron (Fe), copper (Cu), zinc (Zn) and selenium (Se), do not only regulate host immune responses, but modify the viral genome, as well. While low serum Fe concentration is an independent risk factor for the increased death rate, Zn controls oxidative stress, synthesis of inflammatory cytokines and viral replication. Therefore, Zn deficiency associates with a worse prognosis. Although Cu exposure inactivates the viral genome and exhibits spike protein dispersal, increase in Cu/Zn due to high serum Cu levels, are correlated with enhanced risk of infections. Se levels are significantly higher in surviving COVID-19 patients. Meanwhile, both Zn and Se suppress the replication of SARS-CoV-2. Since the balance between the deficiency and oversupply of these metals due to a reciprocal relationship, has decisive effect on the prognosis of the SARS-CoV-2 infection, monitoring their concentrations may facilitate improved outcomes for patients suffering from COVID-19.
... Selenium supplementation also enhances the immune response, reduces oxidative stress, and diminishes the inflammation and the severity of viral behavior [196,205,206]. In addition, there is a hypothesis that selenium supplements may reduce the ability of the SARS-CoV-2 virus to infect human cells [207]. This supplement therapy can increase T cells, especially CD 4 + T cells, and the percentage of NK cells, followed by NK cell cytotoxicity [208]. ...
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COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.
... Selenium (Se), a trace element necessary for human and animal organisms, plays a variety of biological functions in metabolism. Se can participate in the host immune response, reproductive process, and carcinogenesis and regulate the normal operation of the cardiovascular system [1][2][3][4]. Se alleviates the detrimental effects on growth performance and development of immune organs in duck affected by aflatoxin [5]. ...
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To explore the role of ChTLR4/MyD88/NF-κB signaling pathway on autophagy induced by selenium (Se) deficiency in the chicken bursa of Fabricius, autophagosome formation in the bursa of Fabricius was observed by transmission electron microscopy. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of ChTLR4 and its signaling pathway molecules (MyD88, TRIF, and NF-κB), inflammatory factors (IL-1β, IL-8, and TNF-α), and autophagy-related factors (ATG5, Beclin1, and LC3-II) in the Se-deficient chicken bursa of Fabricius at different ages. The results showed that ChTLR4/MyD88/NF-κB signaling pathway was activated in the chicken bursa of Fabricius and autophagy was induced at the same time by Se deficiency. In order to verify the relationship between the autophagy and ChTLR4/MyD88/NF-κB signaling pathway, HD11 cells were used to establish the normal C group, low Se group, and low Se + TLR4 inhibitor (TAK242) group. The results demonstrated that autophagy could be hindered when the TLR4 signaling pathway was inhibited under Se deficiency. Furthermore, autophagy double-labeled adenovirus was utilized to verify the integrity of autophagy flow induced by Se deficiency in HD11 cells. The results showed that it appeared to form a complete autophagy flow under the condition of Se deficiency and could be blocked by TAK242. In summary, we found that Se deficiency was involved in the chicken bursa of Fabricius autophagy occurring by activating the ChTLR4/MyD88/NF-κB pathway.