scholarly journals The Impact of Angiotensin-Converting Enzyme 2 (ACE2) Expression Levels in Patients with Comorbidities on COVID-19 Severity: A Comprehensive Review

2021 ◽  
Vol 9 (8) ◽  
pp. 1692
Author(s):  
Rui Rodrigues ◽  
Sofia Costa de Oliveira
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Cell Receptor ◽  
Converting Enzyme ◽  
Human Organ ◽  
Comprehensive Review ◽  
Angiotensin Converting Enzyme 2 ◽  
Chronic Respiratory Diseases ◽  
Host Cell Receptor ◽  
Obesity And Diabetes ◽  
The Impact

Angiotensin-Converting Enzyme 2 (ACE2) has been proved to be the main host cell receptor for the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic. The SARS-CoV-2 spike (S) protein binds to ACE2 to initiate the process of replication. This enzyme is widely present in human organ tissues, such as the heart and lung. The pathophysiology of ACE2 in SARS-CoV-2 infection is complex and may be associated with several factors and conditions that are more severe in COVID-19 patients, such as age, male gender, and comorbidities, namely, cardiovascular diseases, chronic respiratory diseases, obesity, and diabetes. Here we present a comprehensive review that aims to correlate the levels of expression of the ACE2 in patients with comorbidities and with a poor outcome in COVID-19 disease. Significantly higher levels of expression of ACE2 were observed in myocardial and lung tissues in heart failure and COPD patients, respectively. An age-dependent increase in SARS2-CoV-2 receptors in the respiratory epithelium may be also responsible for the increased severity of COVID-19 lung disease in elderly people. Although the role of ACE2 is highlighted regarding the damage that can arise upon the SARS-CoV-2 invasion, there was no association observed between renin-angiotensin-aldosterone system (RAAS) inhibitors and the severity of COVID-19.

scholarly journals Geranium and Lemon Essential Oils and Their Active Compounds Downregulate Angiotensin-Converting Enzyme 2 (ACE2), a SARS-CoV-2 Spike Receptor-Binding Domain, in Epithelial Cells

Plants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 770 ◽  
Author(s):  
K. J. Senthil Kumar ◽  
M. Gokila Vani ◽  
Chung-Shuan Wang ◽  
Chia-Chi Chen ◽  
Yu-Chien Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Essential Oils ◽  
Cell Receptor ◽  
Gas Chromatography Mass Spectrometry ◽  
Converting Enzyme ◽  
Inhibitory Effects ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Lemon Oil

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease-2019 (COVID-19), is a pandemic disease that has been declared as modern history’s gravest health emergency worldwide. Until now, no precise treatment modality has been developed. The angiotensin-converting enzyme 2 (ACE2) receptor, a host cell receptor, has been found to play a crucial role in virus cell entry; therefore, ACE2 blockers can be a potential target for anti-viral intervention. In this study, we evaluated the ACE2 inhibitory effects of 10 essential oils. Among them, geranium and lemon oils displayed significant ACE2 inhibitory effects in epithelial cells. In addition, immunoblotting and qPCR analysis also confirmed that geranium and lemon oils possess potent ACE2 inhibitory effects. Furthermore, the gas chromatography-mass spectrometry (GC–MS) analysis displayed 22 compounds in geranium oil and 9 compounds in lemon oil. Citronellol, geraniol, and neryl acetate were the major compounds of geranium oil and limonene that represented major compound of lemon oil. Next, we found that treatment with citronellol and limonene significantly downregulated ACE2 expression in epithelial cells. The results suggest that geranium and lemon essential oils and their derivative compounds are valuable natural anti-viral agents that may contribute to the prevention of the invasion of SARS-CoV-2/COVID-19 into the human body.

scholarly journals Increasing Host Cellular Receptor—Angiotensin-Converting Enzyme 2 (ACE2) Expression by Coronavirus may Facilitate 2019-nCoV Infection

2020 ◽  
Author(s):  
Pei-Hui Wang ◽  
Yun Cheng
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Emerging Infectious Diseases ◽  
Cell Receptor ◽  
Host Cells ◽  
Cellular Receptor ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Coronavirus Infection ◽  
Entry Receptor

AbstractThe ongoing outbreak of a new coronavirus (2019-nCoV) causes an epidemic of acute respiratory syndrome in humans. 2019-nCoV rapidly spread to national regions and multiple other countries, thus, pose a serious threat to public health. Recent studies show that spike (S) proteins of 2019-nCoV and SARS-CoV may use the same host cell receptor called angiotensin-converting enzyme 2 (ACE2) for entering into host cells. The affinity between ACE2 and 2019-nCoV S is much higher than ACE2 binding to SARS-CoV S protein, explaining that why 2019-nCoV seems to be more readily transmitted from the human to human. Here, we reported that ACE2 can be significantly upregulated after infection of various viruses including SARS-CoV and MERS-CoV. Basing on findings here, we propose that coronavirus infection can positively induce its cellular entry receptor to accelerate their replication and spread, thus drugs targeting ACE2 expression may be prepared for the future emerging infectious diseases caused by this cluster of viruses.

scholarly journals Mutations in two SARS-CoV-2 variants of concern reflect two distinct strategies of antibody escape

2021 ◽  
Author(s):  
Sebastian Fiedler ◽  
Viola Denninger ◽  
Alexey S. Morgunov ◽  
Alison Ilsley ◽  
Roland Worth ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Cell Receptor ◽  
Converting Enzyme ◽  
Wild Type ◽  
Angiotensin Converting Enzyme 2 ◽  
Binding Domains ◽  
Host Cell Receptor

Understanding the factors that contribute to antibody escape of SARS-CoV-2 and its variants is key for the development of drugs and vaccines that provide broad protection against a variety of virus variants. Using microfluidic diffusional sizing, we determined the dissociation constant ((KD)) for the interaction between receptor binding domains (RBDs) of SARS-CoV-2 in its original version (WT) as well as alpha and beta variants with the host-cell receptor angiotensin converting enzyme 2 (ACE2). For RBD-alpha, the ACE2-binding affinity was increased by a factor of ten when compared with RBD-WT, while ACE2-binding of RBD-beta was largely unaffected. However, when challenged with a neutralizing antibody that binds to both RBD-WT and RBD-alpha with low nanomolar (KD) values, RBD-beta displayed no binding, suggesting a substantial epitope change. In SARS-CoV-2 convalescent sera, RBD-binding antibodies showed low nanomolar affinities to both wild-type and variant RBD proteins—strikingly, the concentration of antibodies binding to RBD-beta was half that of RBD-WT and RBD-alpha, again indicating considerable epitope changes in the beta variant. Our data therefore suggests that one factor contributing to the higher transmissibility and antibody evasion of SARS-CoV-2 alpha and beta is a larger fraction of viruses that can form a complex with ACE2. However, the two variants employ different mechanisms to achieve this goal. While SARS-CoV-2 alpha RBD binds with greater affinity to ACE2 and is thus more difficult to displace from the receptor by neutralizing antibodies, RBD-beta is less accessible to antibodies due to epitope changes which increases the chances of ACE2-binding and infection.

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 Uremic Apelin and Leucocytic Angiotensin-Converting Enzyme 2 in CKD Patients

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 742
Author(s):  
Bogusz Trojanowicz ◽  
Christof Ulrich ◽  
Matthias Girndt
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Healthy Controls ◽  
Converting Enzyme ◽  
Blood Pressure Lowering ◽  
Angiotensin Converting Enzyme 2 ◽  
Pressure Lowering ◽  
The Impact ◽  
Progression Of Atherosclerosis

Apelin peptides (APLN) serve as second substrates for angiotensin-converting enzyme 2 (ACE2) and, in contrast to angiotensin II (AngII), exert blood-pressure lowering and vasodilatation effects through binding to G-coupled APLN receptor (APLNR). ACE2-mediated cleavage of the APLN may reduce its vasodilatory effects, but decreased ACE2 may potentiate the hypotensive properties of APLN. The role of APLN in uremia is unclear. We investigated the correlations between serum-APLN, leucocytic APLNR, and ACE2 in 32 healthy controls (NP), 66 HD, and 24 CKD3–5 patients, and the impact of APLN peptides on monocytic behavior and ACE2 expression under uremic conditions in vitro. We observed that serum APLN and leucocytic APLNR or SLCO2B1 were significantly elevated in uremic patients and correlated with decreased ACE2 on uremic leucocytes. APLN-treated THP-1 monocytes revealed significantly increased APLNR and ACE2, and reduced TNFa, IL-6, and MCSF. Uremic toxins induced a dramatic increase of miR-421 followed by significant reduction of ACE2 transcripts, partially counteracted with APLN-13 and -36. APLN-36 triggered the most potent transmigration and reduction of endothelial adhesion. These results suggest that although APLN peptides may partly protect against the decay of monocytic ACE2 transcripts, uremic milieu is the most dominant modulator of local ACE2, and likely to contribute to the progression of atherosclerosis.

scholarly journals Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor

2020 ◽  
Author(s):  
Sanchita Hati ◽  
Sudeep Bhattacharyya
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Binding Affinity ◽  
Disulfide Bonds ◽  
Host Cells ◽  
Converting Enzyme ◽  
Dynamic Simulations ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
The Impact ◽  
Spike Proteins

AbstractThe novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress.

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 Lions, tigers and kittens too: ACE2 and susceptibility to COVID-19

2020 ◽  
Vol 2020 (1) ◽  
pp. 109-113 ◽  
Author(s):  
Sabateeshan Mathavarajah ◽  
Graham Dellaire
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Cell Receptor ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Specific Manner ◽  
Species Specific ◽  
Computational Analyses

Abstract SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has been reported to infect domesticated animals in a species-specific manner, where cats were susceptible but not dogs. Using the recently published crystal structure of the SARS-CoV-2 spike protein complexed with the human host cell receptor angiotensin converting enzyme 2 (ACE2), we characterized the structure and evolution of ACE2 in several of these species and identify a single interacting amino acid residue conserved between human and Felidae ACE2 but not in Canidae that correlates with virus susceptibility. Using computational analyses we describe how this site likely affects ACE2 targeting by the virus. Thus, we highlight how evolution-based approaches can be used to form hypotheses and study animal transmission of such viruses in the future.

scholarly journals The Impact of Angiotensin-Converting Enzyme 2 (ACE2) Expression on the Incidence and Severity of COVID-19 Infection

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 379
Author(s):  
Ahmed O. Kaseb ◽  
Yehia I. Mohamed ◽  
Alexandre E. Malek ◽  
Issam I. Raad ◽  
Lina Altameemi ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Preventive Measures ◽  
Vulnerable Groups ◽  
The Novel ◽  
Converting Enzyme ◽  
Potential Therapeutic Target ◽  
Angiotensin Converting Enzyme 2 ◽  
Incidence And Mortality ◽  
Novel Coronavirus ◽  
The Impact

The novel coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented threat to the international community and raised major concerns in terms of public health safety. Although our current understanding of the complexity of COVID-19 pathogenesis remains limited, the infection is largely mediated by the interaction of viral spike protein and angiotensin-converting enzyme 2 (ACE2). The functional importance of ACE2 in different demographic and comorbid conditions may explain the significant variation in incidence and mortality of COVID-19 in vulnerable groups, and highlights its candidacy as a potential therapeutic target. We provide evidence supporting the idea that differences in incidence and severity of COVID-19 infection may be related to ACE2. Emerging data based on the prevalence and severity of COVID-19 among those with established high levels of ACE2 expression strongly support our hypothesis. Considering the burden of COVID-19 infection in these vulnerable groups and the impact of the potential therapeutic and preventive measures that would result from adopting ACE2-driven anti-viral strategies, our hypothesis may expedite global efforts to control the current COVID-19 pandemic.

scholarly journals Angiotensin-converting enzyme 2 SNPs as the common genetic loci and optimal early identification genetic markers for COVID-19

2021 ◽  
Author(s):  
Heng Zou ◽  
Qiuyue Li ◽  
Jun Chen ◽  
Songmei Liu ◽  
Shanshan Liu ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Early Identification ◽  
Density Lipoprotein ◽  
Cell Receptor ◽  
Nucleotide Polymorphisms ◽  
Converting Enzyme ◽  
Cardiovascular Risks ◽  
Genetic Loci ◽  
Inflammatory Injury ◽  
Angiotensin Converting Enzyme 2

Abstract Background Angiotensin-converting enzyme 2 (ACE2) is implicated as a host cell receptor that causes infection in the pathogenesis of Coronavirus disease 2019 (COVID-19), and its genetic polymorphisms in the ACE2 gene may promote cardiovascular disease and systemic inflammatory injury in COVID-19. Hence, genetic background may potentially explain the broad inter-individual variation of disease susceptibility and/or severity. Methods The genetic susceptibility to COVID-19 by examining single-nucleotide polymorphisms (SNPs) of ACE2 was analyzed in 196 patients with COVID-19 and 210 normal controls using TaqMan genotyping assay. Results We demonstrated that ACE2 SNP rs4646142, rs6632677, and rs2074192 were associated with COVID-19 (all P < 0.05), and the differences of ACE2 SNPs rs4646142 and rs6632677 were correlated with COVID-19 related systemic inflammatory injury and cardiovascular risk. Specially, rs4646142 was associated with high-sensitive C-reactive protein (hs-CRP), prealbumin (PAB), apolipoprotein A (APOA), high-density lipoprotein (HDL), and acid glycoprotein (AGP). Rs6632677 was also associated with elevated CRP and haptoglobin (HPT). Conclusions Our results suggest that early identification of these individuals can provide a possible strategy for preventing the spread of the COVID-19, and ACE2 SNPs rs4646142 and rs6632677 may be a common genetic loci and optimal early identification genetic marker for COVID-19 with cardiovascular risks.

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