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 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.

Regulation of the Expression of SARS-CoV-2 Receptor Angiotensin-Converting Enzyme 2 in Nasal Mucosa

2021 ◽  
pp. 194589242110277
Author(s):  
Tetsuji Takabayashi ◽  
Kanako Yoshida ◽  
Yoshimasa Imoto ◽  
Robert P. Schleimer ◽  
Shigeharu Fujieda
Keyword(s):  
Epithelial Cells ◽  
Angiotensin Converting Enzyme ◽  
Nasal Mucosa ◽  
Japanese Cedar ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Japanese Cedar Pollen ◽  
Cedar Pollen

Background Coronavirus disease 2019 (COVID-19) has caused a global pandemic. Higher expression of the virus receptor angiotensin-converting enzyme 2 (ACE2) in the nasal mucosa may be associated with high transmissibility and asymptomatic infection. In COVID-19, the elucidation of the determinants of ACE2 expression at nasal tissue level is crucial. The development of strategies to downregulate ACE2 expression in nasal epithelial cells might reduce transmission and be useful as a novel therapeutic approach. Objective To verify ACE2 expression in the nasal mucosa of patients with seasonal allergic rhinitis induced by Japanese cedar pollen (SAR-JCP) and chronic rhinosinusitis with nasal polyp (CRSwNP) and to examine the effects of short-chain fatty acids (SCFAs) on ACE2 expression in airway epithelial cells. Methods We assessed ACE2 expression in the nasal mucosa of control subjects, patients with SAR-JCP, and those with CRSwNP using real-time polymerase chain reaction. We also quantified ACE2 gene expression in cultured airway epithelial cells. Results Although ACE2 expression was greatly increased in a few patients with SAR-JCP during the Japanese cedar pollen season, mean levels were not significantly increased. ACE2 mRNA expression was significantly decreased in nasal polyp tissue from patients with chronic rhinosinusitis compared with the expression in that from control subjects. SCFAs generated by gastrointestinal microbiota significantly reduced resting ACE2 expression in cultured airway epithelial cells. SCFAs also significantly suppressed the dsRNA-dependent upregulation of ACE2 expression in airway epithelial cells. Conclusion Inflammatory endotype affects ACE2 expression in the nasal mucosa and influences susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In particular, type 2 inflammation could downregulate ACE2 expression in the nasal mucosa and reduces susceptibility to SARS-CoV-2 in patients with CRSwNP. Although in vivo experiments are required, administration of SCFAs to the nasal cavity might be worthy of consideration as a preventative or therapeutic strategy for the early-stage COVID-19.

scholarly journals Estrogen regulates the expression of SARS-CoV-2 receptor ACE2 in differentiated airway epithelial cells

2020 ◽  
Vol 318 (6) ◽  
pp. L1280-L1281 ◽  
Author(s):  
Kimberly E. Stelzig ◽  
Fabrizio Canepa-Escaro ◽  
Marta Schiliro ◽  
Sergejs Berdnikovs ◽  
Y. S. Prakash ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Epithelial Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Sex Steroids ◽  
Airway Epithelial Cells ◽  
Cell Entry ◽  
Airway Epithelial ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

There is marked sexual dimorphism in the current coronavirus disease 2019 (COVID-19) pandemic. Here we report that estrogen can regulate the expression of angiotensin-converting enzyme 2 (ACE2), a key component for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry, in differentiated airway epithelial cells. Further studies are required to elucidate the mechanisms by which sex steroids regulate SARS-CoV-2 infectivity.

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 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.

scholarly journals The Significance of Angiotensin-Converting Enzyme-2 (ACE2) in SARSCov-2 Infection and COVID-19

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Carolina Restini ◽  
Trevor Belavek ◽  
Rafael Bernal ◽  
Vanessa Ibrahim ◽  
Kelly Irwin ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Cell Receptor ◽  
Host Cells ◽  
World Health ◽  
Protective Effects ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Health Organization

: The new coronavirus was first reported in 2019 (China) and officially announced by the World Health Organization as a pandemic in March 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pneumonia-associated illnesses and shares structural homology with the related Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1). One of the mechanisms for SARS-Cov-1 and -2 infection is mediated by the angiotensin-converting enzyme-2 (ACE2) cell receptor, enabling the virus to enter the host cells. ACE2 is an isoform of the angiotensin-converting enzyme 1 (ACE). The actions of ACE2 counterbalance the classic renin-angiotensin system (RAS) axis through the production of Ang 1-7, which promotes cardiovascular, renal, and lung-protective effects. The ACE2 is not the only route for SARS-CoV-2 to enter the host cells. However, due to its roles in the RAS and its participation in the SARS-CoV-2 virulence, ACE2 has gained attention regarding viral mechanisms of pathogenesis, effects of drugs that interfere with the RAS, and as a potential target for therapeutic strategies for the damages caused by SARSCoV-2 infection. Among other tissues, ACE2 gene expression seems to be increased in the lungs upon SARS-CoV-2 infection; however, amid other variables, expression and/or activity of ACE2 is shown as a disease, sex, and age-dependent. The present review covers critical aspects for a comprehensive understanding of ACE2 and its current involvement in SARS-CoV-2 infection and the development of COVID-19.

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.

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