scholarly journals Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

2020 ◽  
Author(s):  
Harlan Barker ◽  
Seppo Parkkila
Keyword(s):  
Gene Ontology ◽  
Transcriptional Regulation ◽  
Small Intestine ◽  
Angiotensin Converting Enzyme ◽  
Binding Sites ◽  
Cell Types ◽  
World Health ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

ABSTRACTThe World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 than any other organ. The large intestine, kidney and testis showed moderate signals, whereas the signal was weak in the lung. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.IMPORTANCEVaccines and new medicines are urgently needed to prevent spread of COVID-19 pandemic, reduce the symptoms, shorten the duration of disease, prevent virus spread in the body, and most importantly to save lives. One of the key drug targets could be angiotensin-converting enzyme 2 (ACE2), which is a crucial receptor for the corona virus (SARS-CoV-2). It is known that SARS coronavirus infections lead to worse outcome in the elderly and in males. Therefore, one aim of the present study was to investigate whether age or sex could contribute to the regulation of ACE2 expression. We also decided to explore the transcriptional regulation of ACE2 gene expression. Since data on ACE2 distribution is still conflicting, we aimed to get a more comprehensive view of the cell types expressing the receptor of SARS-CoV-2. Finally, we studied the coexpression of ACE2 with other genes and explored its putative functions using gene ontology enrichment analysis.

scholarly journals Comparison of the COVID-2019 (SARS-CoV-2) pathogenesis with SARS-CoV and MERS-CoV infections

2020 ◽  
Vol 15 (5) ◽  
pp. 317-323 ◽  
Author(s):  
Mona Fani ◽  
Ali Teimoori ◽  
Shokouh Ghafari
Keyword(s):  
Small Intestine ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Target Cells ◽  
Specific Drug ◽  
Converting Enzyme ◽  
Wholesale Market ◽  
Angiotensin Converting Enzyme 2 ◽  
Therapy Options ◽  
Coronavirus Infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in several patients who traveled to Wuhan or went to a seafood wholesale market in Wuhan. The phylogenetic tree showed that SARS-CoV-2 was 96.2% identical to bat β-coronaviruses from lineage B. Also, several studies reported that SARS-CoV-2 uses the SARS-CoV receptor, angiotensin-converting enzyme 2, for entry to target cells. Lung alveolar and small intestine are potential targets for SARS-CoV-2 due to the high expression of the angiotensin-converting enzyme 2 receptor. In this review, we focused on the zoonotic β-coronaviruses and given there is no specific drug or vaccine for coronavirus disease 2019, we reviewed the literature on the therapy options for SARS and Middle East respiratory syndrome coronavirus infection, in order to discover their possible use in the treatment of SARS-CoV-2 infections.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

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.

Angiotensin Converting Enzyme 2 (ACE2) Expression in the Visual System

2021 ◽  
Author(s):  
James M. Hill ◽  
Christian Clement ◽  
L. Arceneaux ◽  
Walter Lukiw
Keyword(s):  
Signal Processing ◽  
Angiotensin Converting Enzyme ◽  
Occipital Lobe ◽  
Cell Types ◽  
Receptor Expression ◽  
Host Cells ◽  
Visual Signal ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
The Brain

Abstract Background: Multiple lines of evidence currently indicate that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)gains entry into human host cells via a high-affinity interaction with the angiotensin-converting enzyme 2 (ACE2) transmembrane receptor. Research has further shown the widespread expression of the ACE2 receptor on the surface of many different immune, non-immune and neural host cell types, and that SARS-CoV-2 has there markable capability to attack many different types of human-host cells simultaneously. One principal neuroanatomical region for highACE2 expression patterns occurs in the brainstem, an area of the brain containing regulatory centers for respiration, and this may in part explain the predisposition of many COVID-19 patients to respiratory distress. Early studies also indicated extensive ACE2 expression in the whole eye and the brain’s visual circuitry. In this study we analyzed ACE2 receptor expression at the mRNA and protein level in multiple cell types involved in human vision, including cell types of the external eye and several deep brain regions known to be involved in the processing of visual signals.Methods: ACE2 mRNA and protein analysis; multiple eye and brain cells and tissues; gamma32P-adenosine tri-phosphate ([γ-32P]dATP) radiolabeled probes; Northern analysis; ELISA.Results: The four main findings were: (i)that many different optical and neural cell types of the human visual system provide receptors essential for SARS-CoV-2 invasion; (ii)the remarkable ubiquity of ACE2 presence in cells of the eye and anatomical regions of the brain involved in visual signal processing; (iii)that ACE2 receptor expression in different ocular cell types and visual processing centers of the brain provide multiple compartments for SARS-CoV-2 infiltration; and (iv)a gradient of increasing ACE2 expression from the anterior surface of the eye to the visual signal processing areas of the occipital lobe and the primary visual neocortex.Conclusion: A gradient of ACE2 expression from the eye surface to the occipital lobe provide the SARS-CoV-2 virus a novel pathway from the outer eye into deeper anatomical regions of the brain involved in vision. These findings may explain, in part, the many recently reported neuro-ophthalmic manifestations of SARS-CoV-2infection in COVID-19 affected patients.

DOCKING STUDY OF NOVEL N-SUBSTITUTED 2,5-BIS[(7-CHLOROQUINOLIN-4-YL)AMINO]PENTANOIC DERIVATIVES AS SELECTIVE HIGH-BINDER WITH ANGIOTENSIN CONVERTING ENZYME 2

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (08) ◽  
pp. 16-24
Author(s):  
Mohammed Oday Ezzat ◽  
Basma M. Abd Razik ◽  
Kutayba F. Dawood
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Active Site ◽  
Docking Study ◽  
World Health ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Pharmaceutical Properties ◽  
Novel Coronavirus

The prevalence of a novel coronavirus (2019-nCoV) in the last few months represents a serious threat as a world health emergency concern. Angiotensin-converting enzyme 2 (ACE2) is the host cellular receptor for the respiratory syndrome of coronavirus epidemic in 2019 (2019-nCoV). In this work, the active site of ACE2 is successfully located by Sitmap prediction tool and validated by different marketed drugs. To design and discover new medical countermeasure drugs, we evaluate a total of 184 molecules of 7-chloro-N-methylquinolin-4-amine derivatives for binding affinity inside the crystal structure of ACE2 located active site. A novel series of N-substituted 2,5-bis[(7-chloroquinolin-4-yl)amino]pentanoic acid derivatives is generated and evaluated for a prospect as a lead compound for (2019-nCoV) medication with a docking score range of (-10.60 to -8.99) kcal/mol for the highest twenty derivatives. Moreover, the ADME pharmaceutical properties were evaluated for further proposed experimental evaluation in vitro or in vivo

scholarly journals Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2)

2020 ◽  
Vol 57 (5) ◽  
pp. 339-350 ◽  
Author(s):  
Annalise E Zemlin ◽  
Owen J Wiese
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
World Health ◽  
Atypical Pneumonia ◽  
Converting Enzyme ◽  
Wholesale Market ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in ‘lockdown’, social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.

scholarly journals A plausible path to contain the spread of 2019 Novel Coronavirus; a computational analysis prompts to the use of ACE2 receptor blockers

2020 ◽  
Author(s):  
Christopher Whitman
Keyword(s):  
Angiotensin Converting Enzyme ◽  
World Health ◽  
Converting Enzyme ◽  
Time Sharing ◽  
Angiotensin Converting Enzyme 2 ◽  
Bioinformatic Tools ◽  
Receptor Blockers ◽  
Genetic Sequences ◽  
Novel Coronavirus ◽  
Health Organization

Abstract Starting December 30th, 2019, a virus spread from Wuhan, in the Hubei Province of China. The virus had soon been recognized as part of the Coronavirus and temporarily named 2019 Novel Coronavirus. The dramatic increase of infections led to the death of over 400 people, by Feb 4th, 2020. By this day the virus had already crossed into 27 countries. March 11th, 2020 the World Health Organization declared the Novel Coronavirus a pandemic, pointing to over 118,000 cases of infections in over 110 countries. This public health threat drove the international community to real-time sharing of the genetic sequences isolated from the viruses. We used these freely accessible genetic data, while leveraging bioinformatic tools, with the intent to explore possible contributions to address this threat. Angiotensin-converting Enzyme 2 Inhibition has been proven to be a valuable strategy address the spread of SARS. After proving remarkable genetic similarities between SARS and the 2019 Novel Coronavirus, we computationally built the first known ex-novo model of the 2019 Novel Coronavirus Spike Glycoprotein entirely generated from its aminoacidic sequence, using I-TASEER. We then assessed the 2019 Novel Coronavirus interaction with the human Angiotensin-converting Enzyme 2. This research prompts at the potential use of Angiotensin- converting Enzyme 2 receptors blockers, as both clinical and prophylaxis measures to contain the spread of 2019 Novel Coronavirus.

scholarly journals COVID-19 and the small intestine

2021 ◽  
Vol 93 (3) ◽  
pp. 343-347
Author(s):  
Sergei D. Bakharev ◽  
Elena V. Baulo ◽  
Svetlana V. Bykova ◽  
Saria R. Dbar ◽  
Asfold I. Parfenov
Keyword(s):  
Small Intestine ◽  
Angiotensin Converting Enzyme ◽  
Oral Route ◽  
The Body ◽  
Entry Point ◽  
Diagnosis And Treatment ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Route Of Infection ◽  
Intestinal Symptoms

The SARS-CoV-2 virus enters the body through the angiotensin-converting enzyme 2 (ACE-2), which is the entry point of the virus into the cell. The most dense fabric of ACE-2 is the lungs. The small intestine also contains large amounts of ACE-2 in the enterocyte membrane and is often involved in this process. Intestinal symptoms can appear at different stages of the disease. The review describes the mechanisms of interaction of SARS-CoV-2 with enterocytes, the fecal-oral route of infection, diagnosis and treatment of COVID-19 with intestinal symptoms.

Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421

2014 ◽  
Vol 127 (4) ◽  
pp. 243-249 ◽  
Author(s):  
Daniel W. Lambert ◽  
Louise A. Lambert ◽  
Nicola E. Clarke ◽  
Nigel M. Hooper ◽  
Karen E. Porter ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Transcriptional Regulation ◽  
Angiotensin Converting Enzyme ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Post Transcriptional Regulation ◽  
Cardiac Myofibroblasts

The molecular mechanisms controlling the expression of ACE2, a critical regulator of cardiovascular homoeostasis, remain poorly defined. In the present study, we show that miR-421 regulates expression of ACE2 in cardiac myofibroblasts, identifying a possible new therapeutic target in cardiovascular disease.

Distinct roles for ANG II and ANG-(1–7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes

2006 ◽  
Vol 290 (2) ◽  
pp. C420-C426 ◽  
Author(s):  
Patricia E. Gallagher ◽  
Mark C. Chappell ◽  
Carlos M. Ferrario ◽  
E. Ann Tallant
Keyword(s):  
Transcriptional Regulation ◽  
Angiotensin Converting Enzyme ◽  
Neonatal Rat ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Neural Responses ◽  
Angiotensin Converting Enzyme 2 ◽  
Rat Astrocytes ◽  
Mediated Reduction ◽  
Angiotensin Type

Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE that preferentially forms angiotensin-(1–7) [ANG-(1–7)] from angiotensin II (ANG II). Incubation of neonatal rat cerebellar or medullary astrocytes with ANG II reduced ACE2 mRNA by ∼60%, suggesting transcriptional regulation of the enzyme. In contrast, ANG II had no effect on ACE mRNA in astrocytes isolated from either brain region, demonstrating a differential regulation of the two enzymes by ANG II. The ANG II-mediated reduction in ACE2 mRNA was blocked by the angiotensin type 1 (AT1) receptor antagonists losartan or valsartan; the angiotensin type 2 (AT2) antagonist PD123319 was ineffective. The reduction in ACE2 mRNA by ANG II also was associated with a 50% decrease in cerebellar and medullary ACE2 protein, which was blocked by losartan. Treatment of medullary astrocytes with ANG-(1–7), the product of ACE2 hydrolysis of ANG II, did not affect ACE2 mRNA; however, ANG-(1–7) prevented the ANG II-mediated reduction in ACE2 mRNA. The addition of [d-Ala7]-ANG-(1–7), a selective AT(1–7) receptor antagonist, blocked the inhibitory actions of ANG-(1–7). These data are the first to demonstrate transcriptional regulation of ACE2 by ANG II and ANG-(1–7). Because ACE2 preferentially converts ANG II to ANG-(1–7), downregulation of the enzyme by ANG II constitutes a novel positive feed-forward system within the brain that may favor ANG II-mediated neural responses. Furthermore, the modulatory role of ANG-(1–7) in the transcriptional regulation of ACE2 by ANG II suggests a complex interplay between these peptides that is mediated by distinct receptor systems.

scholarly journals Identification of gene expression location of angiotensin‐converting enzyme‐2 SNPs as a receptor for SARS‐CoV‐2 in different populations by using various databases

2021 ◽  
Vol 26 (2) ◽  
pp. 101
Author(s):  
Dyah Aryani Perwitasari ◽  
Rita Maliza ◽  
Bayu Tri Murti ◽  
Haafizah Dania ◽  
Athika Darumas Putri
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Binding Capacity ◽  
Treatment Options ◽  
World Health ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Damage Level ◽  
Gene Variation ◽  
Health Organization ◽  
European Populations

The World Health Organization (WHO) has announced that Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) and Coronavirus disease (COVID‐19) is considered a worldwide pandemic. Rapidly rising numbers of patients have been reported in almost every country, along with the growing mortality rates. Uncontrolled growth in patient numbers may be due to reasons such as treatment options and vaccine availabilities and unidentified targets of SARS‐CoV‐2. Previous study has revealed that the molecular target of SARS‐CoV‐2 is analogous to SARS (2003), i.e. angiotensin‐converting enzyme‐2 (ACE‐2). Therefore, the determination of ACE‐2 may enrich existing information and facilitate development of drugs targeted toward SARS‐CoV‐2. This study aims to screen the expression of ACE‐2 genes and their relationship to the types of SNP variants in SARS‐CoV‐2. We explored a series of observations using powerful databases, e.g. GTEx portal, HaploReg, 1000 Genome and Ensembl, to identify the gene variant of ACE‐2. We showed that ACE‐2 is highly expressed in the testes and small intestine, while its lowest level is observed in lymphocytes. Subsequently, we observed 17 gene variants containing a missense mutation potentially damaging protein level. Among these genes, single nucleotide polymorphism (SNP) rs370187012 shows the highest damage‐level score, while the lowest effect is in SNP rs4646116. The highest frequency of the C allele was observed in European populations (1%). In addition to showing that ACE‐2 is expressed in several organs, we concluded that the ACE‐2 gene variation can be found in African, American, Southeast and East Asian, and European populations. The polymorphisms of ACE‐2 impact on the ACE2 protein structure and the binding capacity of the ACE‐2 receptor with the S‐Protein of SARS‐CoV‐2.

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