we are research • Selenium deficiency: a cause of the pathogenicity of viruses • Current information on the pathogen SARS-CoV-2 Selenium deficiency and coronaviruses Selenium is vital to health – it plays an important role in many crucial bodily functions. Certain risk groups are particularly prone to selenium deficiency. The reason can be a lower selenium intake, but also an increased selenium requirement. biosyn know-how selenium deficiency in focus
Transcript
we areresearch
• Selenium deficiency: a cause of the pathogenicity of viruses
• Current information on the pathogen SARS-CoV-2
Selenium deficiency and coronaviruses
Selenium is vital to health – it plays an important role in many crucial bodily functions. Certain risk groups are particularly prone to selenium deficiency. The reason can be a lower selenium intake, but also an increased selenium requirement.
biosyn know-how
selenium deficiency in focus
SELENIUM DEFICIENCY AND CORONAVIRUSES2
Selenium and the coronavirus
In December 2019, a new coronavirus epidemic started in the Chinese city of Wuhan in Hubei province. The new coronavirus is called SARS-CoV-2 and the resulting lung disease is called Covid-19.
Selenium plays a central role in the effectiveness of the body’s defenses in general and with viruses in particular. A selenium deficiency can weaken the immune response to viruses and increase the virulence of certain viruses, including coronaviruses.
SARS-CoV-2
Covid-19
Selenium deficiency
SARS-CoV-2
Infectiousnessof coronaviruses
Seleniumdeficiency
December2019 Covid-19
Created according to:Steinbrenner H et al. Adv Nutr. 2015; 6(1): 73-82. Dietary Selenium in Adjuvant Therapy of Viral and Bacterial Infections.Harthill M. Biol Trace Elem Res. 2011; 143(3): 1325-36. Review: Micronutrient Selenium Deficiency Influences Evolution of Some Viral Infectious Diseases.
In the meantime, the first genome analyses of the new coronavirus SARS-CoV-2 are now available. [1] After comparing the genome sequences of the SARS-CoV-2 pathogen that were isolated from the first nine patients, it is clear that SARS-CoV-2 has only recently emerged or has jumped from animals to humans.
The SARS-CoV-2 belongs to the beta coronaviruses, and there to the subgenus sarbecovirus. The closest relatives among the coronaviruses known so far are the viruses “bat-SL-CoVZC45” and “bat-SL-CoVZXC21” isolated from bats in China, with a sequence match of about 88 percent. The correspondence with the coronaviruses SARS is about 79 percent and MERS only about 50 percent. [1]
Virulence
Changes in the spike protein of the envelope are likely to be decisive for virulence. The virus binds with the S1 domain to the cell membrane, the S2 domain is responsible for the fusion with the cell membrane. These two steps are necessary for the virus to penetrate the cell.
There are striking similarities between SARS-CoV-2 and SARS-CoV, especially in the binding sites of the S1 protein. Wenjie Tan of the China CDC in Beijing therefore assumes that SARS-CoV-2 uses the same entry point as SARS-CoV (Fig. 1).
These include the use of the enzyme ACE2 (“ACE2 cleavage”), which could promote virus uptake, and the use of SARS-S (“SARS-S cleavage”), which activates the S protein for membrane fusion.
SELENIUM DEFICIENCY AND CORONAVIRUSES4
Risk groups
The clinical course of the disease caused by SARS-CoV-2 varies. Some infected persons develop only mild symptoms or none at all. In others, acute lung failure and death occur rapidly. This is shown by the experi-ence of the first 99 patients treated at the Jin Yin-tan Clinic in Wuhan. [2]
According to Li Zhang’s team, most patients were middle-aged (average age 55.5 years). Two-thirds of the patients (67) were male. About half of the diseases (50 cases) occurred in people with underlying chronic condi-tions, including cardiovascular and cerebrovascular diseases (40 patients) and diabetes (12 patients). [2]
How do coronaviruses trigger an infection using the example of SARS-CoV
SARS-Sactivation
SARS-S activation
ACE2TMPRSS2
ADAM17
Infection
Infection
Cathepsin L
H+
SHED
DING
SARS-CoV
SARS-CoV
()
Take-upP
P
P
P
• SARS-CoV S protein = SARS-S• Angiotensin-converting enzyme 2 = ACE2• Type II transmembrane serine protease = TMPRSS2• Metallopeptidase ADAM17 = TACE
Created according to: Heurich A et al. J Virol. 2014; 88(2): 1293-307. TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein.
A selenium deficiency can transform the Coxsackie virus, which is actually harmless to humans, into a danger and possibly trigger Keshan disease, which damages the heart. [3] In the influenza virus, a selenium deficit can lead to mutations that increase its pathogenicity (Fig. 2). [3] The same applies to the SARS virus, which is related to SARS-CoV-2. [4]
Selenium deficiency can increase the virulence of viruses
Mutations*
Higher virulence
SARS-CoV-2?
SARS-CoV
Coxsackie
Ebola
Influenza A
HIV
Seleniumdeficiency
Hepatitis C
* RNA viruses
Created according to:Steinbrenner H et al. Adv Nutr. 2015; 6(1): 73-82. Dietary Selenium in Adjuvant Therapy of Viral and Bacterial Infections.Harthill M. Biol Trace Elem Res. 2011; 143(3): 1325-36. Review: Micronutrient Selenium Deficiency Influences Evolution of Some Viral Infectious Diseases.
Not all details about the coronavirus SARS-CoV-2 are known yet. Inten-sive research has also been carried out on SARS-CoV. The virulence of SARS-CoV is determined by its penetration into the lung cells. The spike glycoprotein is responsible for this. The ACE2 receptor binds with 10 to 20 times higher affinity to the spike binding site of SARS-CoV-2 than to SARS-CoV. This could explain why this virus spreads so easily from per-son to person. [5] In the spike protein of SARS-CoV, two individual amino acid residues at positions 360 and 479 determine the ability to penetrate lung cells. [4]
The intermediate host of SARS-CoV is the civet cat (Paguma larvata). [4] Comparing the coronavirus isolated from the civet cat in the Chinese province of Hubei with the same virus from a civet cat in the province of Guandong, it is striking that the animal coronavirus from Hubei is more closely related to the human SARS-CoV. [4] The difference between the provinces of Hubei and Guandong lies, among other things, in the sele-nium supply. Hubei is a selenium-deficient area, while the selenium con-tent in the soils of Guandong province is adequate (Fig. 3). [4]
Selenium deficiency can increase virulence
The significantly stronger binding to the ACE2 receptor is decisive for the virulence of SARS-CoV-2
SELENIUM DEFICIENCY AND CORONAVIRUSES 7
Does selenium status play a role in the pathogenicity of the SARS coronavirus?
Hubei province(selenium-deficient area)
Guandong province(adequate selenium supply)
SARS-CoVHorseshoe batcoronavirus (CoV)
Civet cat(Civet-CoV)
Higher correspondencewith amino acid residues360 and 479 of the spikeprotein SARS-CoV, whichis crucial for pathogenicity
Created according to: Harthill M. Biol Trace Elem Res. 2011; 143(3): 1325-36. Review: Micro nutrient Selenium Deficiency Influences Evolution of Some Viral Infectious Diseases.
A selenium deficiency can impair the human body’s ability to effectively defend itself against viruses. [6] In addition, a selenium deficiency in viruses can lead to mutations that increase their pathogenicity. [4] Nelson et al. were able to demonstrate a possible mechanism using the example of influenza virus A. [7]
A part of the unspecific humoral immune system is the complement sys-tem. An important part of the complement system is complement C1qA. The viral protein M1 is able to interact with C1qA, thereby preventing complement-mediated neutralization of the influenza virus. [8] Therefore, the M1 protein plays a critical role in protecting the influenza protein from the body’s own innate immune system.
Selenium deficiency can increase the pathogenicity of viruses
The virus protein M1 can increase the virulence of a virus by accelerating its replication. [7] However, the gene for the M1 protein in influenza A viruses is generally stable. [7] In contrast, an increased mutation rate in the M1 gene occurs under selenium deficiency conditions. [7]
The authors attributed this to increased oxidative stress. The influenza virus itself can increase oxidative stress in the host. In combination with increased oxidative stress due to a selenium deficiency-related low activ-ity of the selenium protein glutathione peroxidase-1, this can lead to direct oxidative damage to viral RNA. [7] In the case of selenium deficiency, these mutations can turn a relatively harmless influenza A virus into a much more aggressive influenza A virus (Fig. 4). [7]
A more aggressive influenza A virus due to a selenium deficiency
SELENIUM DEFICIENCY AND CORONAVIRUSES 9
Selenium deficiency weakens the immune system
Influenzavirus
Influenzavirus
Adequateselenium supply
Seleniumdeficiency
Oxidativestress
Virusreplication
Virusreplication
Oxidativestress
ComplementsystemSpecificimmune response
Influenza
ComplementsystemSpecificimmune response
Modified according to: Harthill M. Biol Trace Elem Res. 2011; 143(3): 1325-36. Review: Micronutrient Selenium Deficiency Influences Evolution of Some Viral Infectious Diseases.
Active substance: Sodium selenite pentahydrate. Prescription only
selenase®. Active substance: Sodium selenite pentahydrate. selenase® 100 µg peroral, selenase® T peroral: 50 µg selenium per ml. selenase® 300 Mikrogramm Tabletten: 300 µg selenium per tablet. Indications: selenase® 100 µg peroral, selenase® T peroral: Proven selenium deficiency that cannot be offset from food sources. Selenium deficiencies may occur as a result of states of maldigestion and malabsorption, as well as in malnutrition (e.g. due to complete parenteral nutrition). selenase® 300 Mikrogramm Tabletten: Treatment of clinically proven selenium deficiency that cannot be compensated by nutritional sources, in adults. Composi-tion: selenase® 100 µg peroral: 1 drinking ampoule of 2 ml oral solution contains: 0.333 mg sodium selenite pentahydrate, corresponding to 100 µg (micrograms) selenium. selenase® T peroral: 1 ml oral solution contains: 0.167 mg sodium selenite pentahydrate, corresponding to 50 µg (micrograms) selenium. Excipients: Sodium chloride, hydrochloric acid, water for injections. selenase® 300 Mikrogramm Tabletten: 1 tablet contains 300 microgram selenium as sodium selenite pentahydrate. Excipients: Magnesium stearate (Ph. Eur. vegetable), maize starch, povidone K25, sucrose, talcum. Contra-indications: Hypersensitivity to sodium selenite pentahydrate or to any of the excipients; Selenium poisoning. Undesirable effects: None known to date if the medicinal product is administered according to prescription. Form of administration, size of packages: selenase® 100 µg peroral: : 20, 60, 90 or 100 ampoules of 2 ml oral solution. selenase® T peroral: 10 drinking bottles of 10 ml oral solution plus one measuring cup. selenase® 300 Mikrogramm Tabletten: 20, 50, 100 tablets. Subject to prescription. 01/19 e
1. Lu R et al. Lancet. 2020 Feb 22; 395(10224): 565-74. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.
2. Genom-Analysen klären Herkunft von 2019-nCoV. Deutsches Ärzteblatt. January 30, 2020.
3. Steinbrenner H et al. Adv Nutr. 2015; 6(1): 73-82. Dietary Selenium in Adjuvant Therapy of Viral and Bacterial Infections.
4. Harthill M. Biol Trace Elem Res. 2011; 143(3): 1325-36. Review: Micronutrient Selenium Deficiency Influences Evolution of Some Viral Infectious Diseases.
5. Wrapp D et al. Science. 2020 Feb 19. pii: eabb2507. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
6. Huang Z, Rose AH, Hoffmann PR. Antioxid Redox Signal. 2012 Apr 1; 16(7): 705-43. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities.
7. Nelson HK et al. FASEB J. 2001; 15(10): 1846-8. Host nutritional selenium status as a driving force for influenza virus mutations.
8. Zhang J et al. J Gen Virol. 2009; 90(Pt 11), 2751-8. Influenza A virus M1 blocks the classical complement pathway through interacting with C1qA.
Bibliography
Information on biosyn Arzneimittel GmbH
Selenium deficiency and its consequences
Selenium plays an important role in many important bodily functions. Selenium deficiency is particularly common in certain risk groups. The reason can be a lower selenium intake, but also an increased selenium requirement.
In our “Selenium deficiency in Focus” series, we offer compact information for the most important risk groups for selenium deficiency.
Learn more
Simply order further editions of our topical series by e-mail:[email protected] (please specify desired materials and quantity)
Further information
If you have specific questions on this topic, please call us at: + 49 (0) 711 575 32 - 00
You can also find us on coliquio, the free medical network, with our Infocenter Selenium: www.coliquio.de
• Selenium defi ciency – risk when immune systemis impaired
we areresearch
biosyn know-how
selenium defi ciency in
focus
Selenium is vital to health – it plays an important rolein many crucial bodily functions. Certain risk groups areparticularly prone to selenium deficiency. The reasoncan be a lower selenium intake, but also an increasedselenium requirement.
Selenium deficiency and intensive care patients
• High risk group for selenium deficiency – intensive care patients
• Treatment of selenium deficiency according to guidelines
Selenium is vital to health – it plays an important role in many crucial bodily functions. Certain risk groups are particularly prone to selenium deficiency. The reason can be a lower selenium intake, but also an increased selenium requirement.
Selenium is vital to health – it plays an important role in many crucial bodily functions. Certain risk groups are particularly prone to selenium deficiency. The reason can be a lower selenium intake, but also an increased selenium requirement.
Selenium is vital to health – it plays an important role in many crucial bodily functions. Certain risk groups are particularly prone to selenium deficiency. The reason can be a lower selenium intake, but also an increased selenium requirement.
biosyn know-how
selenium deficiency in
focus
Selenium deficiency and the immune systemFolder for medical expertsSize: A4, 6 pages
Selenium deficiency and intensive care patientsFolder for medical expertsSize: A4, 6 pages
Selenium deficiency and vaccinationsFolder for medical expertsSize: A4, 6 pages
Selenium deficiency and heart diseaseFolder for medical expertsSize: A4, 6 pages
More information about us on our Facebook page, our Twitter and YouTube channel
Managing Director: Dr. Thomas Stiefel and Ortwin KottwitzCommercial Register: County Court Stuttgart HRB 262712Place of performance: Fellbach, Legal venue Stuttgart
