scholarly journals Emerging Role of Neuropilin-1 and Angiotensin-Converting Enzyme-2 in Renal Carcinoma-Associated COVID-19 Pathogenesis

2021 ◽  
Vol 13 (4) ◽  
pp. 902-909
Author(s):  
Md. Golzar Hossain ◽  
Sharmin Akter ◽  
Md Jamal Uddin
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Cell Carcinoma ◽  
Renal Carcinoma ◽  
Expression Profiles ◽  
Host Factor ◽  
Renal Diseases ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Neuropilin 1 ◽  
Increased Risk

Neuropilin-1 (NRP1) is a recently identified glycoprotein that is an important host factor for SARS-CoV-2 infection. On the other hand, angiotensin-converting enzyme-2 (ACE2) acts as a receptor for SARS-CoV-2. Additionally, both NRP1 and ACE2 express in the kidney and are associated with various renal diseases, including renal carcinoma. Therefore, the expression profiles of NRP1 and ACE2 in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) patients from the various cancer databases were investigated along with their impact on patients’ survivability. In addition, coexpression analysis of genes involved in COVID-19, KIRC, and KIRP concerning NRP1 and ACE2 was performed. The results demonstrated that both t NRP1 and ACE2 expressions are upregulated in KIRC and KIRP compared to healthy conditions and are significantly correlated with the survivability rate of KIRC patients. A total of 128 COVID-19-associated genes are coexpressed, which are positively associated with NRP1 and ACE2 both in KIRC and KIRP. Therefore, it might be suggested that, along with the ACE2, high expression of the newly identified host factor NRP1 in renal carcinomas may play a vital role in the increased risk of SARS-CoV-2 infection and survivability of COVID-19 patients suffering from kidney cancers. The findings of this investigation will be helpful for further molecular studies and prevention and/or treatment strategies for COVID-19 patients associated with renal carcinomas.

scholarly journals Target-Centered Drug Repurposing Predictions of Human Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Protease Serine Subtype 2 (TMPRSS2) Interacting Approved Drugs for Coronavirus Disease 2019 (COVID-19) Treatment through a Drug-Target Interaction Deep Learning Model

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1325
Author(s):  
Yoonjung Choi ◽  
Bonggun Shin ◽  
Keunsoo Kang ◽  
Sungsoo Park ◽  
Bo Ram Beck
Keyword(s):  
Deep Learning ◽  
Angiotensin Converting Enzyme ◽  
Drug Target ◽  
Expression Profiles ◽  
Drug Repurposing ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Target Interaction ◽  
Approved Drugs ◽  
Fda Approved Drugs

Previously, our group predicted commercially available Food and Drug Administration (FDA) approved drugs that can inhibit each step of the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI). Unfortunately, additional clinically significant treatment options since the approval of remdesivir are scarce. To overcome the current coronavirus disease 2019 (COVID-19) more efficiently, a treatment strategy that controls not only SARS-CoV-2 replication but also the host entry step should be considered. In this study, we used MT-DTI to predict FDA approved drugs that may have strong affinities for the angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane protease serine 2 (TMPRSS2) which are essential for viral entry to the host cell. Of the 460 drugs with Kd of less than 100 nM for the ACE2 receptor, 17 drugs overlapped with drugs that inhibit the interaction of ACE2 and SARS-CoV-2 spike reported in the NCATS OpenData portal. Among them, enalaprilat, an ACE inhibitor, showed a Kd value of 1.5 nM against the ACE2. Furthermore, three of the top 30 drugs with strong affinity prediction for the TMPRSS2 are anti-hepatitis C virus (HCV) drugs, including ombitasvir, daclatasvir, and paritaprevir. Notably, of the top 30 drugs, AT1R blocker eprosartan and neuropsychiatric drug lisuride showed similar gene expression profiles to potential TMPRSS2 inhibitors. Collectively, we suggest that drugs predicted to have strong inhibitory potencies to ACE2 and TMPRSS2 through the DTI model should be considered as potential drug repurposing candidates for COVID-19.

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 Mutating novel interaction sites in NRP1 reduces SARS-CoV-2 spike protein internalization

2021 ◽  
Author(s):  
Debjani Pal ◽  
Kuntal De ◽  
Tomithy Yates ◽  
Wellington Muchero
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ribosomal Protein ◽  
Protein S ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Interaction Sites ◽  
Viral Binding ◽  
Expression Of Genes ◽  
Neuropilin 1

The global pandemic of Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 has become a severe global health problem because of its rapid spread. Both angiotensin-converting enzyme 2 and neuropilin 1 provide initial viral binding sites for SARS-CoV-2. Here, we show that three cysteine residues located in a1/a2 and b1 domains of neuropilin 1 are necessary for SARS-CoV-2 spike protein internalization in human cells. Mutating cysteines C82, C104, and C147 altered neuropilin 1 stability and binding ability as well as cellular internalization and lysosomal translocation of the spike protein. This resulted in up to 4 times reduction in spike protein load in cells for the original, alpha, and delta SARS-CoV-2 variants even in the presence of the endogenous angiotensin-converting enzyme 2 receptors. Transcriptome analysis of cells transfected with mutated NRP1 revealed significantly reduced expression of genes involved in viral infection and replication, including eight members of the ribosomal protein L, ten members of ribosomal protein S, and five members of the proteasome β subunit family proteins. We also observed higher expression of genes involved in the suppression of inflammation and endoplasmic reticulum-associated degradation. These observations suggest that these cysteines offer viable targets for therapies against COVID-19.

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 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 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 SARS-CoV-2 receptor, angiotensin-converting enzyme 2, is required for human endometrial stromal cell decidualization†

2020 ◽  
Author(s):  
Sangappa B Chadchan ◽  
Pooja Popli ◽  
Vineet K Maurya ◽  
Ramakrishna Kommagani
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Host Cells ◽  
Converting Enzyme ◽  
Endometrial Stromal Cell ◽  
Endometrial Stromal Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Endometrial Stromal Cell ◽  
Increased Risk

Abstract The coronavirus disease 2019 (COVID-19) first appeared in December 2019 and rapidly spread throughout the world. The SARS-CoV-2 virus enters the host cells by binding to the angiotensin-converting enzyme 2 (ACE2). Although much of the focus is on respiratory symptoms, recent reports suggest that SARS-CoV-2 can cause pregnancy complications such as pre-term birth and miscarriages; and women with COVID-19 have had maternal vascular malperfusion and decidual arteriopathy in their placentas. Here, we report that the ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and the expression increases in stromal cells in the secretory phase. It was observed that the ACE2 mRNA and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. Furthermore, HESCs transfected with ACE2-targeting siRNA impaired the full decidualization response, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1. Additionally, in mice during pregnancy, the ACE2 protein was expressed in the uterine epithelial cells, and stromal cells increased through day 6 of pregnancy. Finally, progesterone induced Ace2 mRNA expression in mouse uteri more than vehicle or estrogen. These data establish a role for ACE2 in endometrial physiology, suggesting that SARS-CoV-2 may be able to enter endometrial stromal cells and elicit pathological manifestations in women with COVID-19, including an increased risk of early pregnancy loss.

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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