Abstract
The novel coronavirus disease 2019 (COVID-19) is rapidly expanding and causing many deaths all over the world with the World Health Organization (WHO) declaring a pandemic in March 2020. Current therapeutic options are limited and there is no registered and/or definite treatment or vaccine for this disease or the causative infection, severe acute respiratory coronavirus 2 syndrome (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2), a part of the renin-angiotensin system (RAS), serves as the major entry point into cells for SARS-CoV-2 which attaches to human ACE2, thereby reducing the expression of ACE2 and causing lung injury and pneumonia. Vitamin D, a fat-soluble-vitamin, is a negative endocrine RAS modulator and inhibits renin expression and generation. It can induce ACE2/Ang-(1-7)/MasR axis activity and inhibits renin and the ACE/Ang II/AT1R axis, thereby increasing expression and concentration of ACE2, MasR and Ang-(1-7) and having a potential protective role against acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Therefore, targeting the unbalanced RAS and ACE2 down-regulation with vitamin D in SARS-CoV-2 infection is a potential therapeutic approach to combat COVID-19 and induced ARDS.
Keywords:
COVID-19; angiotensin-converting enzyme 2; vitamin D.
© 2020 John Wiley & Sons, Ltd.
MeSH terms
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Acute Lung Injury / pathology
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Acute Lung Injury / prevention & control*
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Acute Lung Injury / virology
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Angiotensin I / genetics
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Angiotensin I / metabolism
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Angiotensin-Converting Enzyme 2
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Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
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Betacoronavirus / genetics
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Betacoronavirus / metabolism
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Betacoronavirus / pathogenicity*
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COVID-19
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Coronavirus Infections / drug therapy*
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Coronavirus Infections / pathology
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Coronavirus Infections / virology
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Gene Expression Regulation / drug effects
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Humans
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Pandemics
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Peptidyl-Dipeptidase A / genetics*
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Peptidyl-Dipeptidase A / metabolism
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Pneumonia, Viral / drug therapy*
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Pneumonia, Viral / pathology
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Pneumonia, Viral / virology
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Protein Binding
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Proto-Oncogene Mas
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Receptor, Angiotensin, Type 1 / genetics
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Receptor, Angiotensin, Type 1 / metabolism
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Receptors, Virus / antagonists & inhibitors
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Receptors, Virus / genetics*
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Receptors, Virus / metabolism
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Renin-Angiotensin System / drug effects
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SARS-CoV-2
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Severity of Illness Index
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Spike Glycoprotein, Coronavirus / genetics
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Spike Glycoprotein, Coronavirus / metabolism
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Vitamin D / therapeutic use*
Substances
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Angiotensin-Converting Enzyme Inhibitors
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MAS1 protein, human
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Peptide Fragments
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Proto-Oncogene Mas
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Receptor, Angiotensin, Type 1
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Receptors, Virus
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Spike Glycoprotein, Coronavirus
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Vitamin D
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Angiotensin I
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2
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angiotensin I (1-7)