ACE2: The key Molecule for Understanding the Pathophysiology of Severe and Critical Conditions of COVID-19: Demon or Angel?

Viruses. 2020 Apr 28;12(5):491. doi: 10.3390/v12050491.


Recently, the SARS-CoV-2 induced disease COVID-19 has spread all over the world. Nearly 20% of the patients have severe or critical conditions. SARS-CoV-2 exploits ACE2 for host cell entry. ACE2 plays an essential role in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and fluid balance. ACE2 also protects organs from inflammatory injuries and regulates intestinal functions. ACE2 can be shed by two proteases, ADAM17 and TMPRSS2. TMPRSS2-cleaved ACE2 allows SARS-CoV-2 cell entry, whereas ADAM17-cleaved ACE2 offers protection to organs. SARS-CoV-2 infection-caused ACE2 dysfunction worsens COVID-19 and could initiate multi-organ failure. Here, we will explain the role of ACE2 in the pathogenesis of severe and critical conditions of COVID-19 and discuss auspicious strategies for controlling the disease.

Keywords: ACE2; ADAM17; Ang-(1-7); B0AT1; COVID-19; RAAS; SARS-CoV-2; TMPRSS2.

MeSH terms

  • ADAM17 Protein / metabolism
  • Angiotensin-Converting Enzyme 2
  • COVID-19
  • Coronavirus Infections / enzymology
  • Coronavirus Infections / physiopathology*
  • Coronavirus Infections / prevention & control
  • Critical Illness
  • Humans
  • Pandemics / prevention & control
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / enzymology
  • Pneumonia, Viral / physiopathology*
  • Pneumonia, Viral / prevention & control
  • Serine Endopeptidases / metabolism
  • Virus Internalization*


  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • ADAM17 Protein
  • ADAM17 protein, human