scholarly journals Regulation of Angiotensin-Converting Enzyme 2: A Potential Target to Prevent COVID-19?

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Hu ◽  
Lihuan Liu ◽  
Xifeng Lu

The renin–angiotensin system (RAS) is crucially involved in the physiology and pathology of all organs in mammals. Angiotensin-converting enzyme 2 (ACE2), which is a homolog of ACE, acts as a negative regulator in the homeostasis of RAS. ACE2 has been proven to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic. As SARS-CoV-2 enters the host cells through binding of viral spike protein with ACE2 in humans, the distribution and expression level of ACE2 may be critical for SARS-CoV-2 infection. Growing evidence shows the implication of ACE2 in pathological progression in tissue injury and several chronic conditions such as hypertension, diabetes, and cardiovascular disease; this suggests that ACE2 is essential in the progression and clinical prognosis of COVID-19 as well. Therefore, we summarized the expression and activity of ACE2 under various conditions and regulators. We further discussed its potential implication in susceptibility to COVID-19 and its potential for being a therapeutic target in COVID-19.

Author(s):  
Tianshu Xiao ◽  
Jianming Lu ◽  
Jun Zhang ◽  
Rebecca I. Johnson ◽  
Lindsay G.A. McKay ◽  
...  

AbstractEffective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.


2021 ◽  
Author(s):  
Fabrizio Pucci ◽  
Filippo Annoni ◽  
Robson Augusto Souza dos Santos ◽  
Fabio Silvio Taccone ◽  
Marianne Rooman

Abstract The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes. One of its key components, the angiotensin-converting enzyme 2, has been identified as the entry point of the SARS-CoV-2 virus into the host cells, so many studies have been devoted to study RAS dysregulation in COVID-19. Here we discuss the alterations of the regulatory RAS axes due to SARS-CoV-2 infection on the basis of a series of recent clinical and experimental analyzes, which, for example, quantify the levels and activity of RAS components, in order to disentangle the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. Finally, we discussed the effects of some RAS-targeting drugs, and how they could potentially contribute to restore the normal RAS functionality and minimize COVID-19 severity.


2020 ◽  
Vol 33 (1) ◽  
pp. 1-5
Author(s):  
Neiberg de Alcantara Lima ◽  
Pedro Yuri Paiva Lima ◽  
Ricardo Lessa de Castro Junior ◽  
Eric Martin Sieloff ◽  
Stela Maria Vitorino Sampaio

Initially reported in China at the end of 2019, the coronavirus pandemic has now reached an international scale with more than 1.5 million cases worldwide and more than eighty thousands deaths by April 8th of this year. Recent studies have shown that the virus invades host cells by the angiotensin-converting enzyme 2 receptor, making it essential to viral transmission. Concerns have been raised about possible benefits and harms associated with the use of ACE inhibitors and angiotensin receptors blockers in these patients. However, there is lack of evidence to recommend even temporarily discontinuing renin-angiotensin system inhibitors/blockers in patients infected with the SARS-CoV-2.


Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 651-661 ◽  
Author(s):  
Ravindra K. Sharma ◽  
Bruce R. Stevens ◽  
Alexander G. Obukhov ◽  
Maria B. Grant ◽  
Gavin Y. Oudit ◽  
...  

Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B 0 AT1, in gut. But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, severe acute respiratory syndrome coronavirus-2, to infect host cells, similar to severe acute respiratory syndrome coronavirus-2. This suggests that ACE2 be considered harmful, however, because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases, including coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2. This review describes the discovery of ACE2, its physiological functions, and its place in the renin-angiotensin system. It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.


2020 ◽  
Vol 6 (4) ◽  
pp. 248-251 ◽  
Author(s):  
Allegra Battistoni ◽  
Massimo Volpe

Abstract Since December 2019, a new coronavirus, named SARS-CoV-2, has spread globally, affecting >200 000 people worldwide with the so-called COVID-19 disease. The scientific community is actively and constantly working to identify the mechanisms involved in the diffusion of this virus and the pathogenesis of the infection, with its most frequent and severe complication, namely interstitial pneumonia. To date, SARS-CoV-2 is known to enter the host cells via the angiotensin-converting enzyme 2 protein. For this reason, the hypothesis that drugs capable of increasing the expression of this protein may have a role in the spread of the virus and in the symptomatology of affected patients has taken hold. The purpose of this Editorial is to briefly show the evidence currently available in this regard and to provide ideas for future research.


TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.


2020 ◽  
Vol 126 (10) ◽  
pp. 1456-1474 ◽  
Author(s):  
Mahmoud Gheblawi ◽  
Kaiming Wang ◽  
Anissa Viveiros ◽  
Quynh Nguyen ◽  
Jiu-Chang Zhong ◽  
...  

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