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1.
Int J Mol Sci ; 23(4)2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1701976

ABSTRACT

Selenium has been extensively evaluated clinically as a chemopreventive agent with variable results depending on the type and dose of selenium used. Selenium species are now being therapeutically evaluated as modulators of drug responses rather than as directly cytotoxic agents. In addition, recent data suggest an association between selenium base-line levels in blood and survival of patients with COVID-19. The major focus of this mini review was to summarize: the pathways of selenium metabolism; the results of selenium-based chemopreventive clinical trials; the potential for using selenium metabolites as therapeutic modulators of drug responses in cancer (clear-cell renal-cell carcinoma (ccRCC) in particular); and selenium usage alone or in combination with vaccines in the treatment of patients with COVID-19. Critical therapeutic targets and the potential role of different selenium species, doses, and schedules are discussed.


Subject(s)
COVID-19/drug therapy , Neoplasms/drug therapy , Selenium/therapeutic use , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , COVID-19/virology , DNA Repair/drug effects , Drug Resistance, Neoplasm/drug effects , Humans , NF-E2-Related Factor 2/chemistry , NF-E2-Related Factor 2/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Selenium/chemistry , Selenium/metabolism , Selenium/pharmacology
2.
Inflammopharmacology ; 30(2): 499-503, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1681274

ABSTRACT

BACKGROUND: This study aimed to assess tendency of oxidative stress in COVID-19 patients depending on severity. METHODS: The study was conducted with 80 post-COVID-19 disease patients and 40 acutely ill patients. Content of selenium in blood plasma was detected by a fluorimetric method with di-amino-naphthalene using acidic hydrolysis. Selenoprotein P, malondialdehyde and 4-hydroxynonenal and their metabolite adducts were evaluated by spectrophotometric methods using commercial assay kits. RESULTS: Obtained results showed that selenium content in blood for post-COVID-19 disease patients was of a similar lower norm for Latvian inhabitants. Selenium and seleno-protein P contents for acute patients were significantly decreased compared with post-COVID-19 disease patients. CONCLUSION: In conclusion, COVID-19 involves induction of antioxidant systems-in case of severe disease, patients have significantly low concentration of selenium, seleno-protein P and higher level of oxidative stress, which, in turn, confirms the more intense formation of free radicals in the body.


Subject(s)
COVID-19 , Oxidative Stress , SARS-CoV-2 , Selenium , Selenoprotein P , COVID-19/metabolism , Humans , Selenium/metabolism , Selenoprotein P/metabolism
3.
Int J Mol Sci ; 23(2)2022 Jan 12.
Article in English | MEDLINE | ID: covidwho-1638520

ABSTRACT

The selenium field expanded at a rapid rate for about 45 years, from the mid-1970's until about 2015 (see [...].


Subject(s)
Disease Susceptibility , Health Impact Assessment , Homeostasis , Selenium/metabolism , Selenoproteins/metabolism , Humans , Selenium/adverse effects
4.
Molecules ; 26(23)2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1551614

ABSTRACT

Selenium (Se), a microelement essential for life, is critical for homeostasis of several critical functions, such as those related to immune-endocrine function and signaling transduction pathways. In particular, Se is critical for the function of the thyroid, and it is particularly abundant in this gland. Unfortunately, Se deficiency is a very common condition worldwide. Supplementation is possible, but as Se has a narrow safety level, toxic levels are close to those normally required for a correct need. Thus, whether the obtaining of optimal selenium concentration is desirable, the risk of dangerous concentrations must be equally excluded. This review addressed the contribution by environment and food intake on Se circulating levels (e.g., geographical factors, such as soil concentration and climate, and different quantities in food, such as nuts, cereals, eggs, meat and fish) and effects related to its deficiency or excess, together with the role of selenium and selenoproteins in the thyroid pathophysiology (e.g., Hashimoto's thyroiditis and Graves' disease).


Subject(s)
Selenium/metabolism , Selenoproteins/metabolism , Thyroid Gland/metabolism , Animals , Humans
5.
Nat Commun ; 12(1): 3061, 2021 05 24.
Article in English | MEDLINE | ID: covidwho-1387342

ABSTRACT

The SARS-CoV-2 pandemic has triggered global efforts to develop therapeutics. The main protease of SARS-CoV-2 (Mpro), critical for viral replication, is a key target for therapeutic development. An organoselenium drug called ebselen has been demonstrated to have potent Mpro inhibition and antiviral activity. We have examined the binding modes of ebselen and its derivative in Mpro via high resolution co-crystallography and investigated their chemical reactivity via mass spectrometry. Stronger Mpro inhibition than ebselen and potent ability to rescue infected cells were observed for a number of derivatives. A free selenium atom bound with cysteine of catalytic dyad has been revealed in crystallographic structures of Mpro with ebselen and MR6-31-2 suggesting hydrolysis of the enzyme bound organoselenium covalent adduct and formation of a phenolic by-product, confirmed by mass spectrometry. The target engagement with selenation mechanism of inhibition suggests wider therapeutic applications of these compounds against SARS-CoV-2 and other zoonotic beta-corona viruses.


Subject(s)
Azoles/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Organoselenium Compounds/pharmacology , SARS-CoV-2/enzymology , Antiviral Agents/pharmacology , Azoles/chemistry , Catalytic Domain , Coronavirus 3C Proteases/metabolism , Crystallography, X-Ray , Cysteine/chemistry , Hydrolysis , Isoindoles , Models, Molecular , Organoselenium Compounds/chemistry , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Reference Standards , SARS-CoV-2/drug effects , Salicylanilides/chemistry , Salicylanilides/pharmacology , Selenium/metabolism
6.
Int J Mol Sci ; 22(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288904

ABSTRACT

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 µM and 8 µM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile.


Subject(s)
Antiviral Agents/chemistry , Quercetin/chemistry , SARS-CoV-2/metabolism , Selenium/chemistry , Viral Matrix Proteins/antagonists & inhibitors , Animals , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Binding Sites , COVID-19/pathology , COVID-19/virology , Catalytic Domain , Chlorocebus aethiops , Humans , Hydrogen Bonding , Molecular Docking Simulation , Protease Inhibitors/chemistry , Protease Inhibitors/metabolism , Protease Inhibitors/pharmacology , Quercetin/metabolism , Quercetin/pharmacology , SARS-CoV-2/isolation & purification , Selenium/metabolism , Vero Cells , Viral Matrix Proteins/metabolism , Virus Replication/drug effects
7.
Eur Rev Med Pharmacol Sci ; 25(10): 3772-3790, 2021 05.
Article in English | MEDLINE | ID: covidwho-1264762

ABSTRACT

Multiple epidemiological studies have suggested that industrialization and progressive urbanization should be considered one of the main factors responsible for the rising of atherosclerosis in the developing world. In this scenario, the role of trace metals in the insurgence and progression of atherosclerosis has not been clarified yet. In this paper, the specific role of selected trace elements (magnesium, zinc, selenium, iron, copper, phosphorus, and calcium) is described by focusing on the atherosclerotic prevention and pathogenesis plaque. For each element, the following data are reported: daily intake, serum levels, intra/extracellular distribution, major roles in physiology, main effects of high and low levels, specific roles in atherosclerosis, possible interactions with other trace elements, and possible influences on plaque development. For each trace element, the correlations between its levels and clinical severity and outcome of COVID-19 are discussed. Moreover, the role of matrix metalloproteinases, a family of zinc-dependent endopeptidases, as a new medical therapeutical approach to atherosclerosis is discussed. Data suggest that trace element status may influence both atherosclerosis insurgence and plaque evolution toward a stable or an unstable status. However, significant variability in the action of these traces is evident: some - including magnesium, zinc, and selenium - may have a protective role, whereas others, including iron and copper, probably have a multi-faceted and more complex role in the pathogenesis of the atherosclerotic plaque. Finally, calcium and phosphorus are implicated in the calcification of atherosclerotic plaques and in the progression of the plaque toward rupture and severe clinical complications. In particular, the role of calcium is debated. Focusing on the COVID-19 pandemia, optimized magnesium and zinc levels are indicated as important protective tools against a severe clinical course of the disease, often related to the ability of SARS-CoV-2 to cause a systemic inflammatory response, able to transform a stable plaque into an unstable one, with severe clinical complications.


Subject(s)
Atherosclerosis/pathology , Trace Elements/metabolism , Atherosclerosis/metabolism , COVID-19/pathology , COVID-19/virology , Calcium/blood , Calcium/metabolism , Copper/blood , Copper/metabolism , Humans , Iron/blood , Iron/metabolism , Magnesium/blood , Magnesium/metabolism , Matrix Metalloproteinases/metabolism , Phosphorus/blood , Phosphorus/metabolism , Risk , SARS-CoV-2/isolation & purification , Selenium/blood , Selenium/metabolism , Severity of Illness Index , Trace Elements/blood , Zinc/blood , Zinc/metabolism
8.
Redox Biol ; 37: 101709, 2020 10.
Article in English | MEDLINE | ID: covidwho-739131

ABSTRACT

OBJECTIVE: The trace element selenium (Se) is needed for regular biosynthesis of selenoproteins, which contribute to antioxidative defense systems and affect redox-regulated signaling. Elevated Se intake and selenoprotein expression levels have been associated with impaired hydrogen peroxide-dependent signaling by insulin, leading to hyperglycemia and insulin resistance. The relation of low Se intake with glucose status and carbohydrate metabolism is poorly known. RESEARCH DESIGN AND METHODS: A cross sectional analysis among healthy subjects residing in two Chinese counties with different habitual Se intakes was conducted. Fasted glucose levels were related to Se concentrations of 5686 adults by linear regression analysis with Se, body mass index, age, thyroid status, insulin and sex as independent variables. RESULTS: Serum Se correlated strongly and positively with glucose in the Se-deficient population. There was no strong relationship of Se and glucose in the non-deficient population. Overt hypoglycemia (serum glucose < 2.8 mM) was observed in 19.2% of this random sample of subjects in the Se-deficient and in 1.4% of the moderately supplied population, respectively. CONCLUSIONS: An adequate Se supply constitutes an important factor for glucose homeostasis in human subjects. The interaction between Se status and glucose control is not limited to hyperglycemia, but apparently extends to hypoglycemia risk in Se deficiency. This newly identified relationship may be of relevance for the course of severe disease including major trauma, sepsis and COVID-19, where Se deficiency has been associated with mortality risk.


Subject(s)
Blood Glucose/metabolism , Hypoglycemia/metabolism , Selenium/deficiency , Adult , Blood Glucose/analysis , COVID-19/complications , Cross-Sectional Studies , Female , Humans , Hypoglycemia/blood , Hypoglycemia/complications , Male , Middle Aged , Selenium/metabolism
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