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Review
. 2020 Dec;198(6):867-877.
doi: 10.1007/s00408-020-00408-4. Epub 2020 Nov 10.

ACE2: The Major Cell Entry Receptor for SARS-CoV-2

Filippo Scialo  1   2 , Aurora Daniele  3   2 , Felice Amato  4   2 , Lucio Pastore  4   2 , Maria Gabriella Matera  5 , Mario Cazzola  6 , Giuseppe Castaldo  4   2 , Andrea Bianco  1
Affiliations
Review

ACE2: The Major Cell Entry Receptor for SARS-CoV-2

Filippo Scialo et al. Lung. 2020 Dec.

Abstract

Despite the unprecedented effort of the scientific community, the novel SARS-CoV-2 virus has infected more than 46 million people worldwide, killing over one million two hundred thousand. Understanding the mechanisms by which some individuals are more susceptible to SARS-CoV-2 infection and why a subgroup of them are prone to experience severe pneumonia, and death should lead to a better approach and more effective treatments for COVID-19. Here, we focus our attention on ACE2, a primary receptor of SARS-CoV-2. We will discuss its biology, tissue expression, and post-translational regulation that determine its potential to be employed by SARS-CoV-2 for cell entry. Particular attention will be given to how the ACE2 soluble form can have a great impact on disease progression and thus be used in a potential therapeutic strategy. Furthermore, we will discuss repercussions that SARS-CoV-2/ACE2 binding has on the renin-angiotensin system and beyond. Indeed, although mostly neglected, ACE2 can also act on [des-Arg 937]-bradykinin of the kinin-kallikrein system regulating coagulation and inflammation. Thorough comprehension of the role that ACE2 plays in different pathways will be the key to assess the impact that SARS-CoV-2/ACE2 binding has on organismal physiology and will help us to find better therapies and diagnostic tools.

Keywords: ACE2 receptor; COVID-19; SARS-CoV-2.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
SARS-CoV-2 infection and dysregulation of the RAAS and KKS. Sars-CoV-2 binding to the ACE2 receptor can cause its internalization and possible dysregulation of both the RAAS and KKS. Indeed, without the counterbalance action of ACE2, AngII is not converted in Ang1–7 and able to overactivate its receptor AT1R promoting vasoconstriction, production of proinflammatory cytokines such as TNFα, IL6, IL1, and ROS generation through NADPH oxidase. ACE2 also plays a key role in the regulation of the KKS by inactivating LDEABK and DEABK making them incapable to bind the receptor BRB1. The overactivation of BRB1 receptor has been shown to promote inflammation and coagulation
See this image and copyright information in PMC

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