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

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

Natalia Zamorano Cuervo  1 , Nathalie Grandvaux  1   2
Affiliations
Review

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

Natalia Zamorano Cuervo et al. Elife. .

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.

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Conflict of interest statement

NZ, NG No competing interests declared

Figures

Figure 1.
Figure 1.. Angiotensin-converting enzyme 2 (ACE2), the proposed receptor of SARS-CoV-2, is expressed in the respiratory airways at low levels (blue) compared to the intestine, kidney, heart, and pancreas.
Low levels are also observed in the liver. In nasal and bronchial tissues, ACE2 is mainly expressed by ciliated, club, and goblet cells. It is also found in type-2 pneumocytes of alveoli and in endothelial cells of pulmonary capillaries. In comorbidities associated with a severity and poor prognosis of COVID-19, ACE2 levels are increased in the lungs of COPD and smokers and in the heart of patients with cardiovascular diseases (CVD). In contrast, patients with hypertension exhibit decreased levels of ACE2 in the kidney. In T2D patients, ACE2 is decreased in the pancreas and the vascular system but increased in the lungs. Current evidence supports a possible role of co-receptors or attachment factors, such as neuropilins, heparan sulfate, and sialic acids. The low detection of ACE2 in respiratory tissues also led to the speculation of a role of alternative receptors, such as CD147 and GRP78.
See this image and copyright information in PMC

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