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.
© 2020, Zamorano Cuervo and Grandvaux.
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