Antimicrobial and anti-viral effects of selenium nanoparticles and selenoprotein based strategies: COVID-19 and beyond.

Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NFκB), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-ß) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized.

Biogenic Selenium Nanoparticles in Biomedical Sciences: Properties, Current Trends, Novel Opportunities and Emerging Challenges in Theranostic Nanomedicine.

Selenium is an important dietary supplement and an essential trace element incorporated into selenoproteins with growth-modulating properties and cytotoxic mechanisms of action. However, different compounds of selenium usually possess a narrow nutritional or therapeutic window with a low degree of absorption and delicate safety margins, depending on the dose and the chemical form in which they are provided to the organism. Hence, selenium nanoparticles (SeNPs) are emerging as a novel therapeutic and diagnostic platform with decreased toxicity and the capacity to enhance the biological properties of Se-based compounds. Consistent with the exciting possibilities offered by nanotechnology in the diagnosis, treatment, and prevention of diseases, SeNPs are useful tools in current biomedical research with exceptional benefits as potential therapeutics, with enhanced bioavailability, improved targeting, and effectiveness against oxidative stress and inflammation-mediated disorders. In view of the need for developing eco-friendly, inexpensive, simple, and high-throughput biomedical agents that can also ally with theranostic purposes and exhibit negligible side effects, biogenic SeNPs are receiving special attention. The present manuscript aims to be a reference in its kind by providing the readership with a thorough and comprehensive review that emphasizes the current, yet expanding, possibilities offered by biogenic SeNPs in the biomedical field and the promise they hold among selenium-derived products to, eventually, elicit future developments. First, the present review recalls the physiological importance of selenium as an oligo-element and introduces the unique biological, physicochemical, optoelectronic, and catalytic properties of Se nanomaterials. Then, it addresses the significance of nanosizing on pharmacological activity (pharmacokinetics and pharmacodynamics) and cellular interactions of SeNPs. Importantly, it discusses in detail the role of biosynthesized SeNPs as innovative theranostic agents for personalized nanomedicine-based therapies. Finally, this review explores the role of biogenic SeNPs in the ongoing context of the SARS-CoV-2 pandemic and presents key prospects in translational nanomedicine.

The Effect of Selenium on Pathogenicity and Mortality of COVID-19: Focusing on the Biological Role of Selenium

In the last two years, coronavirus infections increased the mortality rate among the elderly and especially patients who suffer from chronic diseases. Despite vaccination, many people are still dying from COVID-19. Among these, the role of minerals in increasing the function of the immune system and combating coronavirus infection has been proven. Selenium (Se) is a crucial valuable element for human health with a determinative in decreasing the amount of ROS produced in response to different viral infections within the body. The role of selenoprotein enzymes in struggling oxidative caused by ROS overproduction is very important. The overall function of cytotoxic cells increases by the presence of selenium. Recent clinical trials carried out on patients with COVID-19 have demonstrated that the deficiency of selenium is obvious in patients who suffer from acute respiratory infections. Due to the role of selenium in viral inflammation, it is expected that this substance will prevent the cytokine storm and ultimately mortality of infected people by reducing the production of inflammatory cytokines. The present study investigates the role of selenium and selenoproteins and their possible mechanisms in the pathogenesis of viral infections. Further comprehension on the the role of the pathogenesis of viral infections and their mortality could be achieved through identifying potential selenoproteins in the COVID 19 genome by means of computational tools. The following core competencies are addressed in this article: The effect of selenium on pathogenicity and mortality of COVID-19.

Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19.

The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them.

Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2.

Viral infections have afflicted human health and despite great advancements in scientific knowledge and technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need to review the evidence on the impact of nutritional strategies to maintain a healthy immune system, particularly in instances where there are limited therapeutic treatments. Selenium, an essential trace element in humans, has a long history of lowering the occurrence and severity of viral infections. Much of the benefits derived from selenium are due to its incorporation into selenocysteine, an important component of proteins known as selenoproteins. Viral infections are associated with an increase in reactive oxygen species and may result in oxidative stress. Studies suggest that selenium deficiency alters immune response and viral infection by increasing oxidative stress and the rate of mutations in the viral genome, leading to an increase in pathogenicity and damage to the host. This review examines viral infections, including the novel SARS-CoV-2, in the context of selenium, in order to inform potential nutritional strategies to maintain a healthy immune system.

Selenium to selenoproteins - role in COVID-19.

The disruption of antioxidant defense has been demonstrated in severe acute respiratory syndrome due to SARS-CoV infection. Selenium plays a major role in decreasing the ROS produced in response to various viral infections. Selenoprotein enzymes are essential in combating oxidative stress caused due to excessive generation of ROS. Selenium also has a role in inhibiting the activation of NF-κB, thus alleviating inflammation. In viral infections, selenoproteins have also been found to inhibit type I interferon responses, modulate T cell proliferation and oxidative burst in macrophages, and inhibit viral transcriptional activators. Potential virally encoded selenoproteins have been identified by computational analysis in different viral genomes like HIV-1, Japanese encephalitis virus (JEV), and hepatitis C virus. This review discusses the role and the possible mechanisms of selenium, selenoproteins, and virally encoded selenoproteins in the pathogenicity of viral infections. Identification of potential selenoproteins in the COVID 19 genome by computational tools will give insights further into their role in the pathogenesis of viral infections.

The Relevance of Plant-Derived Se Compounds to Human Health in the SARS-CoV-2 (COVID-19) Pandemic Era.

Dietary selenium (Se)-compounds accumulated in plants are essential for human metabolism and normal physiological processes. Inorganic and organic Se species can be readily absorbed by the human body, but are metabolized differently and thus exhibit distinct mechanisms of action. They can act as antioxidants or serve as a source of Se for the synthesis of selenoproteins. Selenocysteine, in particular, is incorporated at the catalytic center of these proteins through a specific insertion mechanism and, due to its electronic features, enhances their catalytic activity against biological oxidants. Selenite and other Se-organic compounds may also act as direct antioxidants in cells due to their strong nucleophilic properties. In addition, Se-amino acids are more easily subjected to oxidation than the corresponding thiols/thioethers and can bind redox-active metal ions. Adequate Se intake aids in preventing several metabolic disorders and affords protection against viral infections. At present, an epidemic caused by a novel coronavirus (SARS-CoV-2) threatens human health across several countries and impacts the global economy. Therefore, Se-supplementation could be a complementary treatment to vaccines and pharmacological drugs to reduce the viral load, mutation frequency, and enhance the immune system of populations with low Se intake in the diet.

Selenium.

Selenium (Se) is an element commonly found in the environment at different levels. Its compounds are found in soil, water, and air. This element is also present in raw materials of plant and animal origin, so it can be introduced into human organisms through food. Selenium is a cofactor of enzymes responsible for the antioxidant protection of the body and plays an important role in regulating inflammatory processes in the body. A deficiency in selenium is associated with a number of viral diseases, including COVID-19. This element, taken in excess, may have a toxic effect in the form of joint diseases and diseases of the blood system. Persistent selenium deficiency in the body may also impact infertility, and in such cases supplementation is needed.

Selenium and selenoproteins in viral infection with potential relevance to COVID-19.

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 samples from surviving than non-surviving COVID-19 patients. Furthermore, a significant, positive, linear association was found between the cure rate of Chinese patients with COVID-19 and regional selenium status. Moreover, the cure rate continued to rise beyond the selenium intake required to optimise selenoproteins, suggesting that selenoproteins are probably not the whole story. Nonetheless, the significantly reduced expression of a number of selenoproteins, including those involved in controlling ER stress, along with increased expression of IL-6 in SARS-CoV-2 infected cells in culture suggests a potential link between reduced selenoprotein expression and COVID-19-associated inflammation. In this comprehensive review, we describe the history of selenium in viral infections and then go on to assess the potential benefits of adequate and even supra-nutritional selenium status. We discuss the indispensable function of the selenoproteins in coordinating a successful immune response and follow by reviewing cytokine excess, a key mediator of morbidity and mortality in COVID-19, and its relationship to selenium status. We comment on the fact that the synthetic redox-active selenium compound, ebselen, has been found experimentally to be a strong inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host. That finding suggests that redox-active selenium species formed at high selenium intake might hypothetically inhibit SARS-CoV-2 proteases. We consider the tactics that SARS-CoV-2 could employ to evade an adequate host response by interfering with the human selenoprotein system. Recognition of the myriad mechanisms by which selenium might potentially benefit COVID-19 patients provides a rationale for randomised, controlled trials of selenium supplementation in SARS-CoV-2 infection.