Insights Into the Role of Angiotensin-Converting Enzyme 2 in the Onset of Severe Acute Respiratory Syndrome Coronavirus 2 Pathogenesis

2021 ◽  
pp. 233-252
Author(s):  
Shiv Bharadwaj ◽  
Vivek Dhar Dwivedi ◽  
Sang Gu Kang ◽  
Nikhil Kirtipal ◽  
R. C. Sobti
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

scholarly journals ACE2 the Janus-faced protein – from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19

2020 ◽  
Vol 134 (7) ◽  
pp. 747-750 ◽  
Author(s):  
Rhian M. Touyz ◽  
Hongliang Li ◽  
Christian Delles
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Basic Science ◽  
Physiological Role ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Multifunctional Protein ◽  
Angiotensin Converting Enzyme 2

Abstract Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). It also acts as the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which causes Coronavirus Disease (COVID)-19. In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.

scholarly journals Gastrointestinal and kidney manifestations in SARS-CoV and SARS-CoV-2 infections: role of angiotensin-converting enzyme 2

2020 ◽  
Vol 25 (1) ◽  
pp. 7-20
Author(s):  
Fatemeh Maghool ◽  
◽  
Mohammad Hassan Emami ◽  
Samaneh Mohammadzadeh ◽  
Aida Heidari ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Gastrointestinal Symptoms ◽  
Renin Angiotensin System ◽  
Structural Similarity ◽  
Clinical Feature ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Kidney Impairment

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 2020, which has a substantial structural similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the outbreak in 2003, is currently a threat to global health. Lung involvement is the principal clinical feature in infected patients but extra-pulmonary clinical presentations are also common. The reasons for the extensive involvement of other organs are not yet clear. Angiotensin-converting enzyme 2 (ACE2), the key peptide of renin–angiotensin system (RAS), has recently identified as a major receptor for the both SARS-CoV and SARS-CoV-2 that might be a main target of coronavirus infection. ACE2 is mainly expressed in the pulmonary pneumocytes, the small intestine enterocytes as well as the proximal tubule epithelial cells of the kidneys. In addition to the respiratory tract infection symptoms, the noticeable prevalence of gastrointestinal symptoms as well as kidney impairment in hospitalized infected patients highlights other routes of infection/transmission. In present review, we discussed the role of RAS with emphasis on ACE2 in the pathogenesis of SARS-CoV and SARS-CoV-2, particularly in gastrointestinal and kidney manifestations of the diseases.

scholarly journals Severe Acute Respiratory Syndrome-coronavirus 2 Infection: Role of Angiotensin-converting Enzyme 2

2020 ◽  
Vol 95 (4) ◽  
pp. 232-235
Author(s):  
Jinho Shin
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Human Studies ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Alveolar Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Lung Cells

A role of angiotensin-converting enzyme 2 (ACE2) in the coronavirus disease 2019 pandemic has been suggested, because it is the molecular receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2). ACE2 is known to provide a protective effect for cardiac and vascular tissues, because it generally counteracts angiotensin II (Ang II) activity. ACE2 downregulation has been implicated in the pathogenesis of cardiovascular disease. ACE inhibitors and angiotensin receptor blockers may enhance ACE2 mRNA expression and enzyme activity. However, this has not been demonstrated in lung tissue. In the lungs, Ang II induces vasoconstriction to prevent ventilation perfusion mismatch, while also increasing vascular permeability (which can precipitate pulmonary edema). ACE2 is expressed in 0.67% of human lung cells, 80% of which are type 2 alveolar cells. Men (of all ethnicities) and Asian individuals have been shown to express higher levels of ACE2 than women and non-Asian individuals, respectively. However, there are no data from human studies indicating that high ACE2 expression increases the likelihood of SARS-CoV2 infection. In animal studies, an increase in Ang II caused by SARS-CoV2 or spike protein interactions, in turn due to ACE2 downregulation, has been identified as the key mechanism underlying lung injury. In human studies of SARS-CoV2 infection, ACE2 overexpression was shown to cause inflammatory apoptosis and a cytokine storm. The actions of ACE2 and Ang II in SARS-CoV2-infected vascular and lung tissues differ between animals and humans. ACE2 expression levels pre- and post-SARS-CoV2 infection should be differentiated.

Angiotensin Converting Enzyme-2: A Doorway for SARS-CoV-2

Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Vikas Pandey ◽  
Indu Lata Kanwar ◽  
Tanweer Haider ◽  
Vishal Gour ◽  
Monika Vishwakarma ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Human Body ◽  
Spike Protein ◽  
Specific Method ◽  
The Novel ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus

: The novel coronavirus severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) has become a pandemic, as declared by WHO in March 2020 producing the deleterious effects to patients worldwide. The angiotensin-converting enzyme-2 (ACE-2) has been recognized as the co-receptor for SARS-CoV-2 infections and may acts as a therapeutic step in blocking the enzyme to reduce SARS-CoV-2 expression and further cellular entry. Presently, the role of ACE-2 in coronavirus disease 2019 (COVID-19) infection has been known and the experts have started working on the enzyme ACE-2 for the management and treatment of this pandemic disease. The binding of spike (S) protein of SARS-CoV-2 to these receptors is the most important step and plays a key role in viral replication, thus this enzyme is becoming the doorway for the entry and spread in the human body causing asymptomatic pneumonia and severe of which is leading to death. As no specific method to prevent and treat this disease is available, the use of ACE-2 as a targeting ligand with COVID-19 virus spike protein could be helpful in the proper management of SARS-CoV-2 pneumonia.

scholarly journals Do sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression explain increased severity and mortality of COVID-19 in males?

Diagnosis ◽  
2020 ◽  
Vol 7 (4) ◽  
pp. 385-386 ◽  
Author(s):  
Jens Vikse ◽  
Giuseppe Lippi ◽  
Brandon Michael Henry
Keyword(s):  
Mortality Rate ◽  
Severe Acute Respiratory Syndrome ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Immunomodulatory Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Cytopathic Effects ◽  
Severe Lung

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), shares similarities with the former SARS outbreak, which was caused by SARS-CoV-1. SARS was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. COVID-19 has a higher mortality rate in men both inside and outside China. In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males. We highlight that immunomodulatory treatment must be tailored to the underlying immunobiology at different stages of disease. Moreover, by investigating sex-based immunobiological differences, we may enhance our understanding of COVID-19 pathophysiology and facilitate improved immunomodulatory strategies.

scholarly journals The Use of Fabric Masks in Prevention of Community Transmission of COVID-19

2020 ◽  
Vol 8 (2) ◽  
pp. 168-175
Author(s):  
Rudi Saputra
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Angiotensin Converting Enzyme ◽  
Medical Personnel ◽  
New Disease ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Public Discussion ◽  
The Public ◽  
Community Transmission

Introduction: COVID-19 (Coronavirus Disease 2019) is a new disease due to SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) which can be transmitted through droplets. One effort to prevent transmission of COVID-19 is to use a mask. Medical masks are effective in preventing transmission of COVID-19, but their numbers are very limited and are very much needed by medical personnel when treating COVID-19 patients. Therefore, to prevent the spread of COVID-19 more broadly, alternative medical masks are needed, namely by using cloth masks which have not been discussed much about the purpose of their use to the public. Discussion: SARS-CoV-2 is a cause of COVID-19 and infects the respiratory tract, especially in the lungs (pulmo) through the ACE2 receptor (Angiotensin-Converting Enzyme 2). SARS-CoV-2 has a diameter of around 120 nm. Cloth masks as an alternative to the scarcity of medical masks are recommended for public use. The recommended cloth masks are made of cotton or a cloth towel. A cloth mask is able to hold large droplets (> 5 μm), but not small droplets. Conclusion: Cloth masks can be used by the community in an effort to minimize transmission of COVID-19 by holding large droplets, but it is not effective in preventing transmission of COVID-19 because it can still be passed by SARS-CoV-2. Suggestion: Cloth masks can be optimized using nanoparticles to resist SARS-CoV-2.

scholarly journals Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2

2020 ◽  
Author(s):  
Huihui Mou ◽  
Brian D. Quinlan ◽  
Haiyong Peng ◽  
Yan Guo ◽  
Shoujiao Peng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Viral Receptor ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Binding Domains ◽  
Protein Receptor ◽  
Horseshoe Bat ◽  
Horseshoe Bats

SUMMARYThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme 2 (ACE2). ACE2 is also the viral receptor of SARS-CoV (SARS-CoV-1), a related coronavirus that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus) are presumed to be the original reservoir of both viruses, and a SARS-like coronavirus, RaTG13, closely related SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize the ability of S-protein receptor-binding domains (RBDs) of SARS-CoV-1, SARS-CoV-2, and RaTG13 to bind a range of ACE2 orthologs. We observed that the SARS-CoV-2 RBD bound human, pangolin, and horseshoe bat (R. macrotis) ACE2 more efficiently than the SARS-CoV-1 or RaTG13 RBD. Only the RaTG13 RBD bound rodent ACE2 orthologs efficiently. Five mutations drawn from ACE2 orthologs of nine Rhinolophus species enhanced human ACE2 binding to the SARS-CoV-2 RBD and neutralization of SARS-CoV-2 by an immunoadhesin form of human ACE2 (ACE2-Fc). Two of these mutations impaired neutralization of SARS-CoV-1. An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc. These data narrow the potential SARS-CoV-2 reservoir, suggest that SARS-CoV-1 and -2 originate from distinct bat species, and identify a more potently neutralizing form of ACE2-Fc.

scholarly journals METFORMIN USE IN DIABETES PRIOR TO HOSPITALIZATION: EFFECTS ON MORTALITY IN COVID-19

2020 ◽  
Vol 26 (10) ◽  
pp. 1166-1172
Author(s):  
Jinghong Li ◽  
Qi Wei ◽  
Willis X. Li ◽  
Karen C. McCowen ◽  
Wei Xiong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Clinical Data ◽  
Laboratory Data ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Objective: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population. Methods: Retrospective analyses were performed on de-identified clinical data from a major hospital in Wuhan, China, that included patients with T2DM hospitalized for COVID-19 during the recent epidemic. One hundred and thirty-one patients diagnosed with COVID-19 and T2DM were used in this study. The primary outcome was mortality. Demographic, clinical characteristics, laboratory data, diabetes medications, and respiratory therapy data were also included in the analysis. Results: Of these 131 patients, 37 used metformin with or without other antidiabetes medications. Among the 37 metformin-taking patients, 35 (94.6%) survived and 2 (5.4%) did not survive. The mortality rates in the metformin-taking group versus the non-metformin group were 5.4% (2/37) versus 22.3% (21/94). Using multivariate analysis, metformin was found to be an independent predictor of survival in this cohort ( P = .02). Conclusion: This study reveals a significant association between metformin use and survival in people with T2DM diagnosed with COVID-19. These clinical data are consistent with potential benefits of the use of metformin for COVID-19 patients with T2DM. Abbreviations: ACE2 = angiotensin-converting enzyme 2; AMPK = AMP-activated protein kinase; BMI = body mass index; COVID-19 = coronavirus disease 2019; SARSCoV-2 = severe acute respiratory syndrome coronavirus 2; T2DM = type 2 diabetes mellitus

Identification of the interaction between Angiotensin-converting Enzyme Residues and Severe Acute Respiratory Syndrome Coronavirus 2.

2021 ◽  
Vol 27 ◽  
Author(s):  
Youness Kadil ◽  
Mohammed Mouhcine ◽  
Imane Rahmoune ◽  
Houda Filali
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Methodological Study ◽  
Angiotensin Converting Enzyme 2 ◽  
Enveloped Virus ◽  
Positive Sense ◽  
Contact Residues ◽  
Cell Membrane Protein

Introduction: Coronaviruses are an enveloped virus with a positive-sense single-stranded RNA genome. It has been shown that the viral spike S glycoprotein binds to the cell membrane protein angiotensin-converting enzyme 2 as an invasive process of the virus. The aim of this research is the application of a computational approach in the identification of the interaction residues ACE2 with severe acute respiratory syndrome Coronavirus 2. A methodological study to understand the interactions between SARS CoV2 and ACE2, which is essential for the development of a vaccine and an antiviral. Methods: The S protein is cleaved into two subunits, S1 and S2. S1 contains the receptor-binding domain (RBD) which allows the virus to bind directly to the peptidase domain of ACE2. Results: Our results present the overall differences in contact residues between the different chains, and an alignment between the two SARS Viruses, along with a presentation of similarity between them.Then S2 likely plays a role in membrane fusion. Conclusions : The synthesis of our results appears to provide potentially a rational set of objectives that can help in the development of a SARS-CoV-2 vaccine.

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