Selenium and RNA virus interactions: Potential implications for SARS-CoV-2 infection (COVID-19)

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.

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Neutrophils in respiratory viral infections

Mucosal Immunology ◽

10.1038/s41385-021-00397-4 ◽

2021 ◽

Author(s):

Cecilia Johansson ◽

Freja C. M. Kirsebom

Keyword(s):

Viral Infections ◽

Immune Cell ◽

Respiratory Infections ◽

Fungal Infections ◽

Severe Disease ◽

The Elderly ◽

Viral Control ◽

Immunological Mechanisms ◽

Respiratory Viral Infections ◽

Viral Respiratory Infections

AbstractViral respiratory infections are a common cause of severe disease, especially in infants, people who are immunocompromised, and in the elderly. Neutrophils, an important innate immune cell, infiltrate the lungs rapidly after an inflammatory insult. The most well-characterized effector mechanisms by which neutrophils contribute to host defense are largely extracellular and the involvement of neutrophils in protection from numerous bacterial and fungal infections is well established. However, the role of neutrophils in responses to viruses, which replicate intracellularly, has been less studied. It remains unclear whether and, by which underlying immunological mechanisms, neutrophils contribute to viral control or confer protection against an intracellular pathogen. Furthermore, neutrophils need to be tightly regulated to avoid bystander damage to host tissues. This is especially relevant in the lung where damage to delicate alveolar structures can compromise gas exchange with life-threatening consequences. It is inherently less clear how neutrophils can contribute to host immunity to viruses without causing immunopathology and/or exacerbating disease severity. In this review, we summarize and discuss the current understanding of how neutrophils in the lung direct immune responses to viruses, control viral replication and spread, and cause pathology during respiratory viral infections.

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The relevance of nutrition as a step forward to combat COVID-19

Macedonian Pharmaceutical Bulletin ◽

10.33320/maced.pharm.bull.2020.66.02.006 ◽

2021 ◽

Vol 66 (2) ◽

pp. 53-66

Author(s):

Zoran Zhivikj ◽

Tanja Petreska Ivanovska ◽

Lidija Petrushevska-Tozi

Keyword(s):

Immune System ◽

Unsaturated Fatty Acids ◽

Viral Infections ◽

Rna Virus ◽

The Elderly ◽

Nutrition Intervention ◽

Human Immune System ◽

Ongoing Research ◽

Prophylactic Measure ◽

Balanced Diet

A new type of single-stranded RNA virus that belongs to the coronavirus’s family named SARS-CoV-2 has recently appeared, with fast-growing human to human transmissions. This virus has posed an important global health threat. Many nutrients can support the immune system and help in preventing or in ameliorating the response to viral infections. In the case of COVID-19, the unique pathophysiology of the coronavirus needs to be understood, in order to determine whether any potential nutrition intervention is indicated. A literature survey that comprised of ongoing research was conducted to evaluate the benefits of the bioactives present in food, such as: plant-derived extracts, vitamins, minerals, probiotics, and prebiotics, against the mechanisms of the COVID-19 infection. Although no food is yet confirmed to help in the prevention or in the treatment of the coronavirus transmission alone, exploring the possible implications of nutrition-infection interrelationships is of utmost importance. Well-designed and controlled clinical studies are emerging to explain whether the higher consumption of fruits, vegetables, protein-rich foods, unsaturated fatty acids, and other natural functional foods may aid in combating the COVID-19 infection. Meanwhile, a healthy and balanced diet is traditionally practised in viral infections that support the healthy gut microbiota profile. The human immune system function should be a vital prophylactic measure, along with adequate physical activities and sleeping habits. The consumption of immune-supportive nutrients is also encouraged in the elderly, comorbid, and in the immune-compromised as well as in malnourished individuals, in order to minimise the complications and the negative outcomes that are associated with the COVID-19 disease. Keywords: COVID-19 nutrition, mаcronutrients, micronutrients, bioactive compounds, malnutrition

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Identification of a Novel Susceptibility Marker for SARS-CoV-2 Infection in Human Subjects and Risk Mitigation with a Clinically Approved JAK Inhibitor in Human/Mouse Cells

10.1101/2020.12.09.416586 ◽

2020 ◽

Author(s):

Marianne R. Spalinger ◽

Rong Hai ◽

Jiang Li ◽

Alina N. Santos ◽

Tara M. Nordgren ◽

...

Keyword(s):

Viral Entry ◽

Viral Infections ◽

Risk Mitigation ◽

Human Subjects ◽

Severe Disease ◽

The Elderly ◽

Jak Inhibitor ◽

Risk Variant ◽

Mouse Cells ◽

Increased Susceptibility

ABSTRACTCoronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020; www.who.int)1. While fatality rates are higher among the elderly and those with underlying comorbidities2, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases.3–7 We report that the autoimmune PTPN2 risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry mediated by SARS-CoV-2 spike protein. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib. Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk.

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Acquired haemophilia in the elderly is a severe disease: report of five new cases

Haemophilia ◽

10.1046/j.1365-2516.2001.00531.x ◽

2001 ◽

Vol 7 (4) ◽

pp. 428-432 ◽

Cited By ~ 20

Author(s):

S. Godreuil ◽

R. Navarro ◽

P. Quittet ◽

L. Landreau ◽

J-F. Schved ◽

...

Keyword(s):

Severe Disease ◽

The Elderly ◽

Acquired Haemophilia

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Highlighting the Correlation Between Telomere Shortening and the Susceptibility to the Novel SARS-CoV-2 Virus (COVID-19)

10.31730/osf.io/k86p3 ◽

2020 ◽

Author(s):

Aml Ghanem

Keyword(s):

Telomere Length ◽

Stress Responses ◽

Viral Infections ◽

Deep Understanding ◽

The Elderly ◽

The Novel ◽

Telomere Shortening ◽

Infection Pathways ◽

And Gender ◽

Demographic Distribution

COVID-19 is a global crisis that requires a deep understanding of infection pathways to facilitate the development of effective treatments and vaccines. Telomere, which is regarded as a biomarker for other respiratory viral infections, might influence the demographic distribution of COVID-19 infection and fatality rates. Viral infection can induce many cellular remodeling events and stress responses, including telomere specific alterations, just as telomere shortening. In brief, this letter aims to highlight the connection between telomere shortening and susceptibility to COVID-19 infection, in addition to changes in telomeric length according to the variation of age and gender of confirmed cases with COVID-19 infection. To sum up, the correlation is revealed from the available data that connect telomere length and COVID-19 infection, demonstrated in the fact that the elderly patients and males are more susceptible to COVID-19 due to shortening in their telomere length.

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Polymyalgia Rheumatica - a Disease of the Elderly

Revista de Chimie ◽

10.37358/rc.18.1.6063 ◽

2018 ◽

Vol 69 (1) ◽

pp. 152-154

Author(s):

Vasilica Cristescu ◽

Aurelia Romila ◽

Luana Andreea Macovei

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Polymyalgia Rheumatica ◽

Temporal Arteritis ◽

Viral Infections ◽

Clinical Manifestations ◽

The Elderly ◽

Clinical Aspects ◽

Immune Disorder ◽

Markers Of Inflammation

Polymyalgia rheumatica is a disease that occurs mostly in the elderly and is rarely seen in patients less than 50 years of age. Polymyalgia rheumatica is a vasculitis, which manifests itself as an inflammatory disease of the vascular wall that can affect any type of blood vessel, regardless of its size. It has been considered a form of giant cell arteritis, involving primarily large and medium arteries and to a lesser extent the arterioles. Clinical manifestations are caused by the generic pathogenic process and depend on the characteristics of the damaged organ. PMR is a senescence-related immune disorder. It has been defined as a stand-alone condition and a syndrome referred to as rheumatic polyarteritis with manifestations of giant cell arteritis (especially in cases of Horton�s disease and temporal arteritis) which are commonly associated with polymyalgia. The clinical presentation is clearly dominated by the painful girdle syndrome, with a feeling of general discomfort. Polymyalgia and temporal arteritis may coexist or be consecutive to each other in the same patient, as in most of our patients. The present study describes 3 cases of polymyalgia rheumatica, admitted to the Clinic of Rheumatology of Sf. Apostol Andrei Hospital, Galati. The cases were compared with the literature. Two clinical aspects (polymyalgia rheumatica and/or Horton�s disease) and the relationship between them were also considered. Polymyalgia rheumatica is currently thought to have a multifactorial etiology, in which the following factors play a role: genetic factors or hereditary predisposition (some individuals are more prone to this disease), immune factors and viral infections (triggers of the disease). Other risk factors of polymyalgia rheumatica include age over 50 years and the association with giant cell arteritis. The characteristic feature of the disease is girdle pain, with intense stiffness of at least one hour�s duration. Markers of inflammation, erythrocyte sedimentation rate and C-reactive protein are almost always increased at the onset of the disease. Diseases that can mimic the clinical picture of polymyalgia rheumatica are neoplasia, infections, metabolic disorders of the bone and endocrine diseases.

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Metapneumovirus humano: epidemiología y posibles tratamientos profilácticos

Studies in the Economic History of Southern Africa ◽

10.22201/fm.24484865e.2020.63.3.02 ◽

2020 ◽

Vol 63 (3) ◽

pp. 7-18

Author(s):

Marcela Solís-Rodríguez ◽

Ángel G. Alpuche-Solís ◽

Rocío G. Tirado-Mendoza

Keyword(s):

Antigenic Determinant ◽

Prophylactic Treatment ◽

Respiratory Infections ◽

Rna Virus ◽

The Elderly ◽

Etiologic Agent ◽

Host Immunity ◽

Acute Respiratory Infections ◽

Antiviral Peptides ◽

Fusion Glycoprotein

In 2001 in the Netherlands, Human metapneumovirus (hMPV) was identified as a “new” etiologic agent causing acute respiratory infections in children younger than 5 years old; however, it has also been isolated in the elderly and immunocompromised people. This virus is considered the second etiological agent in acute diseases of the respiratory tract. Currently, the estimated cost of IRAs in our country is of 9,000USD per inpatient. hMPV is a member of the genus Metapneumovirus, family Pneumoviridae, and it belongs to the order Mononegavirales that is part of the negative single-stranded ribonucleic acid (RNA) virus, consisting of eight genes ordered: 3’-N-P-M-FM2-SH-G-L-5 ‘, and which encodes for 9 proteins. Of these proteins, the F fusion glycoprotein is highly conserved in the genus Metapneumovirus, and is the major antigenic determinant, and because an approved vaccine doesn’t exist, it has been used as a candidate epitope for the design of a vaccine that confers host immunity or as a therapeutic target in the creation of antiviral peptides that inhibit the fusion of the virus to its target cell and to avoid infection in subjects at high risk of contagion since there is currently none accepted by COFEPRIS as a prophylactic treatment against hMPV. Key words: hMPV; respiratory infections; epitopes; protein F;vaccines.

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Human Coronaviruses: Counteracting the Damage by Storm

Viruses ◽

10.3390/v13081457 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1457

Author(s):

Dewald Schoeman ◽

Burtram C. Fielding

Keyword(s):

Immune Response ◽

Severe Disease ◽

Antiviral Agents ◽

The Elderly ◽

Highly Pathogenic ◽

Vaccine Responses ◽

Cell Mediated Immune Response ◽

Inhibition Antibody ◽

A Cell ◽

Human Coronaviruses

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

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Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71

Viruses ◽

10.3390/v13050774 ◽

2021 ◽

Vol 13 (5) ◽

pp. 774

Author(s):

Chengfeng Gao ◽

Chunxia Wen ◽

Zhifeng Li ◽

Shuhan Lin ◽

Shu Gao ◽

...

Keyword(s):

Broad Spectrum ◽

Zika Virus ◽

Therapeutic Agent ◽

Viral Infections ◽

Rna Virus ◽

Emerging Viruses ◽

Enterovirus A71 ◽

Ic50 Values ◽

High Doses ◽

Severe Fever

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

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Poxviral Strategies to Overcome Host Cell Apoptosis

Pathogens ◽

10.3390/pathogens10010006 ◽

2020 ◽

Vol 10 (1) ◽

pp. 6

Author(s):

Chathura D. Suraweera ◽

Mark G. Hinds ◽

Marc Kvansakul

Keyword(s):

Viral Infections ◽

B Cell Lymphoma ◽

Intrinsic Apoptosis ◽

Host Cell Apoptosis ◽

Successful Infection ◽

Infected Cells ◽

Host Virus Interactions ◽

Almost All ◽

Virus Interactions ◽

Multicellular Organisms

Apoptosis is a form of cellular suicide initiated either via extracellular (extrinsic apoptosis) or intracellular (intrinsic apoptosis) cues. This form of programmed cell death plays a crucial role in development and tissue homeostasis in multicellular organisms and its dysregulation is an underlying cause for many diseases. Intrinsic apoptosis is regulated by members of the evolutionarily conserved B-cell lymphoma-2 (Bcl-2) family, a family that consists of pro- and anti-apoptotic members. Bcl-2 genes have also been assimilated by numerous viruses including pox viruses, in particular the sub-family of chordopoxviridae, a group of viruses known to infect almost all vertebrates. The viral Bcl-2 proteins are virulence factors and aid the evasion of host immune defenses by mimicking the activity of their cellular counterparts. Viral Bcl-2 genes have proved essential for the survival of virus infected cells and structural studies have shown that though they often share very little sequence identity with their cellular counterparts, they have near-identical 3D structures. However, their mechanisms of action are varied. In this review, we examine the structural biology, molecular interactions, and detailed mechanism of action of poxvirus encoded apoptosis inhibitors and how they impact on host–virus interactions to ultimately enable successful infection and propagation of viral infections.

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