scholarly journals Regulation of angiotensin converting enzyme 2 (ACE2) in obesity: implications for COVID-19

2020 ◽  
Author(s):  
Saba Al Heialy ◽  
Mahmood Hachim ◽  
Abiola Senok ◽  
Ahmad Abou Tayoun ◽  
Rifat Hamoudi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Angiotensin Converting Enzyme ◽  
Viral Entry ◽  
Pulmonary Inflammation ◽  
Lipid Synthesis ◽  
Lung Epithelial Cells ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Obesity And Diabetes ◽  
Increased Risk

AbstractThe ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene which is involved in regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow completion of their viral replication cycles. Furthermore, a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs which negatively correlated with the expression of genes that code for sterol response element binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Together our results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.

scholarly journals The Effects of Aβ1-42 Binding to the SARS-CoV-2 Spike Protein S1 Subunit and Angiotensin-Converting Enzyme 2

2021 ◽  
Vol 22 (15) ◽  
pp. 8226
Author(s):  
John Tsu-An Hsu ◽  
Chih-Feng Tien ◽  
Guann-Yi Yu ◽  
Santai Shen ◽  
Yi-Hsuan Lee ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Viral Entry ◽  
Negative Impact ◽  
Spike Protein ◽  
Infection Model ◽  
Converting Enzyme ◽  
Viral Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
People With Dementia ◽  
The Impact

Increasing evidence suggests that elderly people with dementia are vulnerable to the development of severe coronavirus disease 2019 (COVID-19). In Alzheimer’s disease (AD), the major form of dementia, β-amyloid (Aβ) levels in the blood are increased; however, the impact of elevated Aβ levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aβ1-42, but not Aβ1-40, bound to various viral proteins with a preferentially high affinity for the spike protein S1 subunit (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the viral receptor, angiotensin-converting enzyme 2 (ACE2). These bindings were mainly through the C-terminal residues of Aβ1-42. Furthermore, Aβ1-42 strengthened the binding of the S1 of SARS-CoV-2 to ACE2 and increased the viral entry and production of IL-6 in a SARS-CoV-2 pseudovirus infection model. Intriguingly, data from a surrogate mouse model with intravenous inoculation of Aβ1-42 show that the clearance of Aβ1-42 in the blood was dampened in the presence of the extracellular domain of the spike protein trimers of SARS-CoV-2, whose effects can be prevented by a novel anti-Aβ antibody. In conclusion, these findings suggest that the binding of Aβ1-42 to the S1 of SARS-CoV-2 and ACE2 may have a negative impact on the course and severity of SARS-CoV-2 infection. Further investigations are warranted to elucidate the underlying mechanisms and examine whether reducing the level of Aβ1-42 in the blood is beneficial to the fight against COVID-19 and AD.

scholarly journals Angiotensin-converting enzyme 2: a double-edged sword in COVID-19 patients with an increased risk of heart failure

2020 ◽  
Author(s):  
Iman Razeghian-Jahromi ◽  
Mohammad Javad Zibaeenezhad ◽  
Zhibing Lu ◽  
Elyaspour Zahra ◽  
Razmkhah Mahboobeh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk

scholarly journals Prerequisites for Improving the Anti-epidemic Regime in Medical Organizations in the Context of the COVID-19 Pandemic

2020 ◽  
Vol 3 (38) ◽  
pp. 17-20
Author(s):  
Assel Khassenova ◽  
◽  
Zaituna Khamidullina ◽  
Zhuldyz Danbayeva ◽  
Gulnoza Aldabekova ◽  
...  
Keyword(s):  
Health Care ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Contact Mode ◽  
Angiotensin Converting Enzyme 2 ◽  
Oral Transmission ◽  
Leading Role ◽  
Increased Risk ◽  
Rapid Spread ◽  
Mode Of Transmission

Abstract The pandemic of COVID-19 remained the central issue for public health due to the rapid spread and high contagiousness of the virus. In Kazakhstan, anti-epidemic measures developed and implemented came as sufficient prevention, which provides the prevention of airborne and contact mode of transmission. However, there are studies that indicated the existence of a fecal-oral mode of transmission due to the presence of angiotensin converting enzyme 2 (ACE2) on the surface of cells of the gastrointestinal tract. Health care workers are at a significantly increased risk of infection because they are in constant contact with potential sources of viral infection. The personnel of medical organizations play a leading role in the fight against the pandemic; the task of the health care system is to create conditions for maintaining and strengthening their health. Considering persisting risks, it is necessary to foresee possible routes of transmission of infection and strengthen the anti-epidemic measurements, taking into account the fecal-oral mode of transmission. Key words: COVID-19, anti-epidemic measures, nosocomial infection, fecal-oral transmission, angiotensin converting enzyme 2 (ACE2), Kazakhstan.

scholarly journals Emerging highlights from novel human coronavirus and angiotensin-converting enzyme 2: promising way to target brain vascular diseases

2020 ◽  
Vol 10 (4) ◽  
pp. 130-134
Author(s):  
Caroline Bozzetto Ambrosi
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Treatment Strategies ◽  
Vascular Diseases ◽  
Human Cells ◽  
Converting Enzyme ◽  
Human Coronavirus ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk ◽  
Almost All ◽  
Open The Doors

A specific metallopeptidase called angiotensin-converting enzyme 2 (ACE2) has been identified as the modulating receptor on the surface of the endothelium and other human cells infected by the new coronavirus causing Severe Acute Respiratory Syndrome (SARS-CoV-2) and Human Coronavirus Disease 2019 (COVID -19). This modulation of the expression of ACE2 in human cells may be responsible for the production of pro-inflammatory response with the development of the state of the systemic response of the inflammatory system, hypercoagulability/stasis also an increased risk of both ischemic and hemorrhagic strokes. Therefore, like ACE2, despite being present in almost all human organs, its expression is variable and probably dependent on epigenetic polymorphism, then this is still to be better understood. However, this highlights the importance to understand its pathogenesis and open the doors for the development of future treatment strategies aimed at various diseases related to ACE2, mainly cerebral vascular diseases, and perhaps COVID-19 itself.

scholarly journals Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
James R. Byrnes ◽  
Xin X. Zhou ◽  
Irene Lui ◽  
Susanna K. Elledge ◽  
Jeff E. Glasgow ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Viral Entry ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Block Interaction ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Receptor

ABSTRACT As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread around the world, there is an urgent need for new assay formats to characterize the humoral response to infection. Here, we present an efficient, competitive serological assay that can simultaneously determine an individual’s seroreactivity against the SARS-CoV-2 Spike protein and determine the proportion of anti-Spike antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. In this approach based on the use of enzyme-linked immunosorbent assays (ELISA), we present natively folded viral Spike protein receptor-binding domain (RBD)-containing antigens via avidin-biotin interactions. Sera are then competed with soluble ACE2-Fc, or with a higher-affinity variant thereof, to determine the proportion of ACE2 blocking anti-RBD antibodies. Assessment of sera from 144 SARS-CoV-2 patients ultimately revealed that a remarkably consistent and high proportion of antibodies in the anti-RBD pool targeted the epitope responsible for ACE2 engagement (83% ± 11%; 50% to 107% signal inhibition in our largest cohort), further underscoring the importance of tailoring vaccines to promote the development of such antibodies. IMPORTANCE With the emergence and continued spread of the SARS-CoV-2 virus, and of the associated disease, coronavirus disease 2019 (COVID-19), there is an urgent need for improved understanding of how the body mounts an immune response to the virus. Here, we developed a competitive SARS-CoV-2 serological assay that can simultaneously determine whether an individual has developed antibodies against the SARS-CoV-2 Spike protein receptor-binding domain (RBD) and measure the proportion of these antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. Using this assay and 144 SARS-CoV-2 patient serum samples, we found that a majority of anti-RBD antibodies compete for ACE2 binding. These results not only highlight the need to design vaccines to generate such blocking antibodies but also demonstrate the utility of this assay to rapidly screen patient sera for potentially neutralizing antibodies.

scholarly journals Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

2021 ◽  
Vol 7 ◽  
Author(s):  
Jacob Roberts ◽  
Antonia L. Pritchard ◽  
Andrew T. Treweeke ◽  
Adriano G. Rossi ◽  
Nicole Brace ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Angiotensin Converting Enzyme ◽  
Inflammatory Responses ◽  
Severe Form ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Inflammatory Processes ◽  
Meta Analyses

Meta-analyses have indicated that individuals with type 1 or type 2 diabetes are at increased risk of suffering a severe form of COVID-19 and have a higher mortality rate than the non-diabetic population. Patients with diabetes have chronic, low-level systemic inflammation, which results in global cellular dysfunction underlying the wide variety of symptoms associated with the disease, including an increased risk of respiratory infection. While the increased severity of COVID-19 amongst patients with diabetes is not yet fully understood, the common features associated with both diseases are dysregulated immune and inflammatory responses. An additional key player in COVID-19 is the enzyme, angiotensin-converting enzyme 2 (ACE2), which is essential for adhesion and uptake of virus into cells prior to replication. Changes to the expression of ACE2 in diabetes have been documented, but they vary across different organs and the importance of such changes on COVID-19 severity are still under investigation. This review will examine and summarise existing data on how immune and inflammatory processes interplay with the pathogenesis of COVID-19, with a particular focus on the impacts that diabetes, endothelial dysfunction and the expression dynamics of ACE2 have on the disease severity.

scholarly journals Effects of Renin-Angiotensin Inhibition on ACE2 and TMPRSS2 Expression: Insights into COVID-19

2020 ◽  
Author(s):  
Congqing Wu ◽  
Dien Ye ◽  
Adam E. Mullick ◽  
Zhenyu Li ◽  
A.H. Jan Danser ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Viral Entry ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Mrna Abundance ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Increase Risk

AbstractAngiotensin-converting enzyme 2 (ACE2), a component of the renin-angiotensin system, is a receptor for SARS-CoV-2, the virus that causes COVID-19. To determine whether the renin-angiotensin inhibition regulates ACE2 expression, either enalapril (an angiotensin-converting enzyme inhibitor) or losartan (an AT1 receptor blocker) was infused subcutaneously to male C57BL/6J mice for two weeks. Neither enalapril nor losartan changed abundance of ACE2 mRNA in lung, ileum, kidney, and heart. Viral entry also depends on transmembrane protease serine 2 (TMPRSS2) to prime the S protein. TMPRSS2 mRNA was abundant in lungs and ileum, modest in kidney, but barely detectable in heart. TMPRSS2 mRNA abundance was not altered by either enalapril or losartan in any of the 4 tissues. Next, we determined whether depletion of angiotensinogen (AGT), the unique substrate of the renin-angiotensin system, changes ACE2 and TMPRSS2 mRNA abundance. AGT antisense oligonucleotides (ASO) were injected subcutaneously to male C57BL/6J mice for 3 weeks. Abundance of ACE2 mRNA was unchanged in any of the 4 tissues, but TMPRSS2 mRNA was significantly decreased in lungs. Our data support that the renin-angiotensin inhibition does not regulate ACE2 and hence are not likely to increase risk for COVID-19.

Molecular characterization of COVID-19 therapeutics: Luteolin as an allosteric modulator of the spike protein of SARS-CoV-2

2021 ◽  
Author(s):  
Juan J de Pablo ◽  
Walter Alvarado ◽  
Fabian Bylehn ◽  
Cintia Menendez ◽  
Gustavo Perez
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Characterization ◽  
Receptor Binding ◽  
Viral Entry ◽  
Spike Protein ◽  
Allosteric Modulator ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

The interactions between the receptor binding domain (RBD) of SARS-CoV-2 and the angiotensin- converting enzyme 2 (ACE2) are crucial for viral entry and subsequent replication. Given the large and featureless...

scholarly journals Identification of the SARS-CoV-2 Entry Receptor ACE2 as a Direct Target for Transcriptional Repression by Miz1

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Yang ◽  
Edith A. Perez ◽  
Changchun Hou ◽  
Pin Zhang ◽  
Michelle Van Scoyk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Cigarette Smoke ◽  
Lung Epithelial Cells ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Copd Patients ◽  
Lung Epithelial

Multiple lines of evidence have demonstrated that cigarette smoke or Chronic Obstructive Pulmonary Disease upregulates angiotensin-converting enzyme 2, the cellular receptor for the entry of the severe acute respiratory syndrome coronavirus 2, which predisposes individuals to develop severe Coronavirus disease 2019. The reason for this observation is unknown. We recently reported that the loss of function of Miz1 in the lung epithelium in mice leads to a spontaneous COPD-like phenotype, associated with upregulation of angiotensin-converting enzyme 2. We also reported that cigarette smoke exposure downregulates Miz1 in lung epithelial cells and in mice, and Miz1 is also downregulated in the lungs of COPD patients. Here, we provide further evidence that Miz1 directly binds to and represses the promoter of angiotensin-converting enzyme 2 in mouse and human lung epithelial cells. Our data provide a potential molecular mechanism for the upregulation of angiotensin-converting enzyme 2 observed in smokers and COPD patients, with implication in severe Coronavirus disease 2019.

scholarly journals Combination of Angiotensin (1-7) Agonists and Convalescent Plasma as a New Strategy to Overcome Angiotensin Converting Enzyme 2 (ACE2) Inhibition for the Treatment of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Hawraa Issa ◽  
Ali H. Eid ◽  
Bassam Berry ◽  
Vahideh Takhviji ◽  
Abbas Khosravi ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Viral Infection ◽  
Viral Entry ◽  
The Body ◽  
Protective Effects ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Neutralizing Capacity ◽  
New Strategy

Coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most concerning health problem worldwide. SARS-CoV-2 infects cells by binding to angiotensin-converting enzyme 2 (ACE2). It is believed that the differential response to SARS-CoV-2 is correlated with the differential expression of ACE2. Several reports proposed the use of ACE2 pharmacological inhibitors and ACE2 antibodies to block viral entry. However, ACE2 inhibition is associated with lung and cardiovascular pathology and would probably increase the pathogenesis of COVID-19. Therefore, utilizing ACE2 soluble analogs to block viral entry while rescuing ACE2 activity has been proposed. Despite their protective effects, such analogs can form a circulating reservoir of the virus, thus accelerating its spread in the body. Levels of ACE2 are reduced following viral infection, possibly due to increased viral entry and lysis of ACE2 positive cells. Downregulation of ACE2/Ang (1-7) axis is associated with Ang II upregulation. Of note, while Ang (1-7) exerts protective effects on the lung and cardiovasculature, Ang II elicits pro-inflammatory and pro-fibrotic detrimental effects by binding to the angiotensin type 1 receptor (AT1R). Indeed, AT1R blockers (ARBs) can alleviate the harmful effects associated with Ang II upregulation while increasing ACE2 expression and thus the risk of viral infection. Therefore, Ang (1-7) agonists seem to be a better treatment option. Another approach is the transfusion of convalescent plasma from recovered patients with deteriorated symptoms. Indeed, this appears to be promising due to the neutralizing capacity of anti-COVID-19 antibodies. In light of these considerations, we encourage the adoption of Ang (1-7) agonists and convalescent plasma conjugated therapy for the treatment of COVID-19 patients. This therapeutic regimen is expected to be a safer choice since it possesses the proven ability to neutralize the virus while ensuring lung and cardiovascular protection through modulation of the inflammatory response.

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