ACE2: Evidence of role as entry receptor for SARS-CoV-2 and implications in comorbidities

Elife. 2020 Nov 9:9:e61390. doi: 10.7554/eLife.61390.

Abstract

Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus 19 disease (COVID-19) which presents a large spectrum of manifestations with fatal outcomes in vulnerable people over 70-years-old and with hypertension, diabetes, obesity, cardiovascular disease, COPD, and smoking status. Knowledge of the entry receptor is key to understand SARS-CoV-2 tropism, transmission and pathogenesis. Early evidence pointed to angiotensin-converting enzyme 2 (ACE2) as SARS-CoV-2 entry receptor. Here, we provide a critical summary of the current knowledge highlighting the limitations and remaining gaps that need to be addressed to fully characterize ACE2 function in SARS-CoV-2 infection and associated pathogenesis. We also discuss ACE2 expression and potential role in the context of comorbidities associated with poor COVID-19 outcomes. Finally, we discuss the potential co-receptors/attachment factors such as neuropilins, heparan sulfate and sialic acids and the putative alternative receptors, such as CD147 and GRP78.

Keywords: ACE2; COVID-19; SARS-CoV-2; cell biology; comorbidities; receptor; virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Basigin / physiology
  • Betacoronavirus / physiology*
  • COVID-19
  • Comorbidity
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / virology*
  • Endoplasmic Reticulum Chaperone BiP
  • Gene Expression Regulation, Enzymologic
  • Heparitin Sulfate / physiology
  • Humans
  • Hypertension / epidemiology
  • Hypertension / physiopathology
  • Neuropilin-1 / physiology
  • Oligopeptides / physiology
  • Organ Specificity
  • Pandemics
  • Peptidyl-Dipeptidase A / physiology*
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / virology*
  • Protein Binding
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Virus
  • Renin-Angiotensin System / physiology
  • Respiratory System / enzymology
  • SARS-CoV-2
  • Sialic Acids / physiology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / physiology
  • Virus Attachment*
  • Virus Internalization

Substances

  • BSG protein, human
  • Bax-inhibiting peptide, BIP
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • NRP1 protein, human
  • Oligopeptides
  • RNA, Messenger
  • Receptors, Virus
  • Sialic Acids
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Basigin
  • Neuropilin-1
  • Heparitin Sulfate
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2