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
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Angiotensin-Converting Enzyme 2
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Basigin / physiology
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Betacoronavirus / physiology*
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COVID-19
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Comorbidity
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Coronavirus Infections / epidemiology
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Coronavirus Infections / virology*
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Endoplasmic Reticulum Chaperone BiP
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Gene Expression Regulation, Enzymologic
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Heparitin Sulfate / physiology
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Humans
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Hypertension / epidemiology
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Hypertension / physiopathology
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Neuropilin-1 / physiology
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Oligopeptides / physiology
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Organ Specificity
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Pandemics
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Peptidyl-Dipeptidase A / physiology*
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Pneumonia, Viral / epidemiology
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Pneumonia, Viral / virology*
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Protein Binding
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Receptors, Virus
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Renin-Angiotensin System / physiology
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Respiratory System / enzymology
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SARS-CoV-2
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Sialic Acids / physiology
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Spike Glycoprotein, Coronavirus / chemistry
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Spike Glycoprotein, Coronavirus / physiology
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Virus Attachment*
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Virus Internalization
Substances
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BSG protein, human
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Bax-inhibiting peptide, BIP
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Endoplasmic Reticulum Chaperone BiP
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HSPA5 protein, human
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NRP1 protein, human
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Oligopeptides
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RNA, Messenger
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Receptors, Virus
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Sialic Acids
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Spike Glycoprotein, Coronavirus
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spike protein, SARS-CoV-2
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Basigin
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Neuropilin-1
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Heparitin Sulfate
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2