The Yin and Yang of ACE/ACE2 Pathways: The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients

Cells. 2020 Jul 16;9(7):1704. doi: 10.3390/cells9071704.

Abstract

The article describes the rationale for inhibition of the renin-angiotensin system (RAS) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent positive feedback-loop mechanisms. Based purely on experimental studies in which RAS pathway inhibitors were administered in vivo to humans/rodents, a reasonable hypothesis of using inhibitors that block both ACE and ACE2 zinc metalloproteases and their downstream pathways in COVID-19 patients will be proposed. In particular, metal (zinc) chelators and renin inhibitors may work alone or in combination to inhibit the positive feedback loops (initially triggered by SARS-CoV-2 and subsequently sustained by hypoxia independently on viral trigger) as both arms of renin-angiotensin system are upregulated, leading to critical, advanced and untreatable stages of the disease.

Keywords: IL-10; Mas receptor; asthma; cardiac dysfunction; eosinophil; hypertension; hypoxia; lung fibrosis; renin-angiotensin system; severe acute respiratory syndrome coronavirus-2.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Angiotensins / metabolism
  • Betacoronavirus / drug effects*
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / physiopathology*
  • Feedback, Physiological / drug effects
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A / adverse effects
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / physiopathology*
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / genetics
  • Renin-Angiotensin System / physiology
  • Risk Factors
  • SARS-CoV-2

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensins
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2