Focus on clinical practice: angiotensin-converting enzyme 2 and corona virus disease 2019: pathophysiology and clinical implications

2020 ◽  
Vol 21 (9) ◽  
pp. 630-633 ◽  
Author(s):  
Francesco Barillà ◽  
Pier Paolo Bassareo ◽  
Giuseppe Calcaterra ◽  
Francesco Romeo ◽  
Jawahar L. Mehta
Keyword(s):  
Clinical Practice ◽  
Angiotensin Converting Enzyme ◽  
Virus Disease ◽  
Clinical Implications ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Corona Virus

scholarly journals ACE2 Nascence, Trafficking and SARS-CoV-2 Pathogenesis: The Saga Continues

2020 ◽  
Author(s):  
Sally Badawi ◽  
Bassam Ali
Keyword(s):  
Cell Surface ◽  
Angiotensin Converting Enzyme ◽  
Virus Disease ◽  
The Novel ◽  
Converting Enzyme ◽  
Post Translational Modifications ◽  
Angiotensin Converting Enzyme 2 ◽  
Viral Attachment ◽  
Corona Virus ◽  
Potential Use

With the emergence of the novel corona virus SARS-CoV-2 since December 2019, more than 43 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases leading to over 1 million deaths globally. Despite the collaborative and concerted research efforts that has been made, no effective treatment for COVID-19 (corona virus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to achieve this through the use of angiotensin converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2. However, through this review, we present another perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, shedding and its cellular trafficking pathways including internalization are not well elucidated. Therefore, hereby we present an overview on the fate of newly synthesized ACE2, its post translational modifications, what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Extensive understanding of these processes is necessary to evaluate the potential use of ACE2 as a credible therapeutic target.

scholarly journals In Depth Review of COVID-19 Effect on CVS

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Rutvi Delvadiya ◽  
Bansi Jagani ◽  
Ankita Gohel ◽  
Jay Desai ◽  
Darshit Ram
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitor ◽  
Virus Disease ◽  
Acute Myocarditis ◽  
Angiotensin Receptor Blockers ◽  
Cardiac Effect ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Corona Virus ◽  
Number Of Patients

Corona virus disease 2019 (covid-19) is global pandemic affecting 185 countries and > 30,00,000 patient worldwide as of April 28,2020 COVID-19 is caused by severe acute respiratory syndrome corona virus. Which invades cells through the angiotensin – converting enzyme 2 receptor. Among patient with COVID-19, there is a high prevalence of cardiovascular disease and > 7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin – converting enzyme 2 serves as the portal for infection, the role of angiotensin – converting enzyme inhibitor or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection. Immunosuppression and posttransplant management. Primary cardiac manifestation includes acute myocarditis, myocardial infarction, arrhythmia and abnormal clotting. The disease does not discrimate but increasing age & the presence of comorbidities are associated with severe form of the disease and poor outcomes. While our knowledge of COVID-19 continues to rapidly expend, this review highlights recent advances in our understanding of the interaction between COVID-19 & the cardiovascular system. Management of acute COVID-19 cardiovascular syndrome should involve a multidisciplinary team including intensive care specialists, infectious disease specialists and cardiologists. Clinical and diagnostic details of cardiovascular involvement in these patients a mostly limited to biochemical markers. Cardiovascular drugs the cardiac effect of therapeutic agent on the illness continue to be under investigation with an increasing number of patients newer promising therapies and ongoing clinical trials the exact mechanisms & extent to which this risk. Factors contribute to outcomes will be clearer in the future.

scholarly journals Renin–Angiotensin–Aldosterone System Inhibitors in Patients with COVID-19: General Considerations and Clinical Implications

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
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Viral Transmission ◽  
Host Cells ◽  
Angiotensin Receptors ◽  
Clinical Implications ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

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.

scholarly journals Targeting Virus-Host Interaction: An in Silico Approach to Develop Promising Inhibitors Against COVID-19

2020 ◽  
Author(s):  
Jitendra Subhash Rane ◽  
Aroni Chatterjee ◽  
Rajni Khan ◽  
Abhijeet Kumar ◽  
Shashikant Ray
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Virus Disease ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Host Cell Membrane ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Interaction

The entire human population all over the globe is currently facing appalling conditions due to<br>the spread of infection from COVID-19 (corona virus disease-2019). In the last few months<br>enormous amount of studies have been continuously trying to target several potential drug<br>sites to identify a novel therapeutic target. Spike protein of severe acute respiratory syndrome<br>coronavirus 2 (SARS-CoV-2) is also being targeted by several scientific groups as a novel<br>drug target. The spike glycoprotein protein is present on the surface of the virion and binds to<br>the human angiotensin-converting enzyme-2 (hACE2) membrane receptor thereby promoting<br>its fusion to the host cell membrane. The binding and internalization of the virus is a crucial<br>step in the process of infection and hence any molecule that can inhibit this, certainly holds a<br>significant therapeutic value. We have identified AP-NP (2-(2-amino-5-(naphthalen-2-<br>yl)pyrimidin-4-yl)phenol) and AP-4-Me-Ph (2-(2-amino-5-(p-tolyl)pyrimidin-4-yl)phenol)<br>from a group of diaryl pyrimidine derivatives which appear to bind at the interface of<br>hACE2-SARS-CoV-2S complex (human angiotensin converting enzyme 2 and spike<br>glycoprotein complex) with a low binding energy (<-8 Kcal/mol). In this in-silico study we<br>also found that AP-NP interacts with S1 domain of C-terminal part of SARS-CoV-2S<br>however AP-4-Me-Ph was found to interact with S2 domain of SARS-CoV-2S. The result<br>suggested that AP-NP and AP-4-Me-Ph have potential to inhibit the interaction between<br>spike protein and hACE2 receptor also AP-4-Me-Ph might be prevent internalization of the<br>virion within the host. Further in vitro and in vivo study will strengthen these drug candidates<br>against the COVID-19. <br>

scholarly journals Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor

2020 ◽  
Author(s):  
Xiangyu Chen ◽  
Ren Li ◽  
Zhiwei Pan ◽  
Chunfang Qian ◽  
Yang Yang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Angiotensin Converting Enzyme ◽  
Virus Disease ◽  
Pseudotyped Virus ◽  
Converting Enzyme ◽  
Human Monoclonal Antibodies ◽  
Human Mabs ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). To date, no prophylactic vaccines or approved therapeutic agents are available for preventing and treating this highly transmittable disease. Here we report two monoclonal antibodies (mAbs) cloned from memory B cells of patients recently recovered from COVID-19, and both mAbs specifically bind to the spike (S) protein of SARS-CoV-2, block the binding of receptor binding domain (RBD) of SARS-CoV-2 to human angiotensin converting enzyme 2 (hACE2), and effectively neutralize S protein-pseudotyped virus infection. These human mAbs hold the promise for the prevention and treatment of the ongoing pandemic of COVID-19.

scholarly journals Targeting Virus-Host Interaction: An in Silico Approach to Develop Promising Inhibitors Against COVID-19

2020 ◽  
Author(s):  
Jitendra Subhash Rane ◽  
Aroni Chatterjee ◽  
Rajni Khan ◽  
Abhijeet Kumar ◽  
Shashikant Ray
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Virus Disease ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Host Cell Membrane ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Interaction

The entire human population all over the globe is currently facing appalling conditions due to<br>the spread of infection from COVID-19 (corona virus disease-2019). In the last few months<br>enormous amount of studies have been continuously trying to target several potential drug<br>sites to identify a novel therapeutic target. Spike protein of severe acute respiratory syndrome<br>coronavirus 2 (SARS-CoV-2) is also being targeted by several scientific groups as a novel<br>drug target. The spike glycoprotein protein is present on the surface of the virion and binds to<br>the human angiotensin-converting enzyme-2 (hACE2) membrane receptor thereby promoting<br>its fusion to the host cell membrane. The binding and internalization of the virus is a crucial<br>step in the process of infection and hence any molecule that can inhibit this, certainly holds a<br>significant therapeutic value. We have identified AP-NP (2-(2-amino-5-(naphthalen-2-<br>yl)pyrimidin-4-yl)phenol) and AP-4-Me-Ph (2-(2-amino-5-(p-tolyl)pyrimidin-4-yl)phenol)<br>from a group of diaryl pyrimidine derivatives which appear to bind at the interface of<br>hACE2-SARS-CoV-2S complex (human angiotensin converting enzyme 2 and spike<br>glycoprotein complex) with a low binding energy (<-8 Kcal/mol). In this in-silico study we<br>also found that AP-NP interacts with S1 domain of C-terminal part of SARS-CoV-2S<br>however AP-4-Me-Ph was found to interact with S2 domain of SARS-CoV-2S. The result<br>suggested that AP-NP and AP-4-Me-Ph have potential to inhibit the interaction between<br>spike protein and hACE2 receptor also AP-4-Me-Ph might be prevent internalization of the<br>virion within the host. Further in vitro and in vivo study will strengthen these drug candidates<br>against the COVID-19. <br>

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