A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19

Rev Med Virol. 2020 Sep;30(5):e2119. doi: 10.1002/rmv.2119. Epub 2020 Jun 25.

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.

Publication types

  • Review

MeSH terms

  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control*
  • Acute Lung Injury / virology
  • Angiotensin I / genetics
  • Angiotensin I / metabolism
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Betacoronavirus / genetics
  • Betacoronavirus / metabolism
  • Betacoronavirus / pathogenicity*
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Gene Expression Regulation / drug effects
  • Humans
  • Pandemics
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • Protein Binding
  • Proto-Oncogene Mas
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, Virus / antagonists & inhibitors
  • Receptors, Virus / genetics*
  • Receptors, Virus / metabolism
  • Renin-Angiotensin System / drug effects
  • SARS-CoV-2
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vitamin D / therapeutic use*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • MAS1 protein, human
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Receptor, Angiotensin, Type 1
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Vitamin D
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)