scholarly journals Coronavirus uses as binding site in humans angiotensin‐converting enzyme 2 functional receptor that is involved in arterial blood pressure control and fibrotic response to damage and is a drug target in cardiovascular disease. Is this just a phylogenetic coincidence?

2020 ◽  
Vol 92 (10) ◽  
pp. 1713-1714 ◽  
Author(s):  
Michele M. Ciulla
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Angiotensin Converting Enzyme ◽  
Drug Target ◽  
Pressure Control ◽  
Converting Enzyme ◽  
Fibrotic Response ◽  
Angiotensin Converting Enzyme 2 ◽  
Arterial Blood ◽  
Functional Receptor

COVID-19 y su asociación con los inhibidores de la enzima convertidora de angiotensina y los antagonistas de los receptores para angiotensina II

2020 ◽  
Vol 63 (4) ◽  
pp. 30-34 ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Angiotensin Converting Enzyme ◽  
Channel Blockers ◽  
Type I ◽  
Converting Enzyme ◽  
Alveolar Cells ◽  
Obstructive Pulmonary Disease ◽  
Angiotensin Converting Enzyme 2 ◽  
Functional Receptor

Worldwide, over 7 million people have been infected due to the pandemic of COVID-19. The comorbidities associated to this disease are: hypertension, diabetes mellitus, obesity, obstructive pulmonary disease (COPD), cardiovascular disease, chronic renal failure, smoking, immunosuppression, and hypertension. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2. This virus has an S protein that recognizes ACE2 as its receptor to enter the cell. ACE2 is a plasmatic protein expressed in alveolar cells type I, II, fibroblasts, endothelial cells and macrophages. Treatment with inhibitors of the angiotensin-converting enzyme (ACEi) or the receptor antagonist for angiotensin II (ARBs) notably increase the expression of ACE2. Therefore, in patients with these pathologies and treated with these medicines, the risk of developing the COVID-19 in a severe and fatal way could be increased. In Mexico, the major mortality due to COVID-19 is related to hypertension, diabetes mellitus, obesity and being over 65 years of age. Therefore, we suggest that during the SARS-CoV-2 pandemic, patients with hypertension treated with ACEi or ARBs, should receive alternative treatments such as L-type Ca2+ channel blockers (amlodipine) that have not been associated with ACE2 until now. Key words: COVID-19; SARS-CoV-2; captopril; losartan hypertension."

scholarly journals Overexpression of Central ACE2 (Angiotensin-Converting Enzyme 2) Attenuates the Pressor Response to Chronic Central Infusion of Ang II (Angiotensin II)

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1514-1525
Author(s):  
Anyun Ma ◽  
Lie Gao ◽  
Ahmed M. Wafi ◽  
Li Yu ◽  
Tara Rudebush ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Pressor Response ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Intracerebroventricular Infusion

We investigated the mechanism by which ACE2 (angiotensin-converting enzyme 2) overexpression alters neurohumoral outflow and central oxidative stress. Nrf2 (nuclear factor [erythroid-derived 2]-like 2) is a master antioxidant transcription factor that regulates cytoprotective and antioxidant genes. We hypothesized that upregulation of central ACE2 inhibits the pressor response to Ang II (angiotensin II) by reducing reactive oxygen species through a Nrf2/antioxidant enzyme–mediated mechanism in the rostral ventrolateral medulla. Synapsin human Angiotensin Converting Enzyme 2 positive (SynhACE2 +/+ ) mice and their littermate controls synhACE2 −/− were used to evaluate the consequence of intracerebroventricular infusion of Ang II. In control mice, Ang II infusion evoked a significant increase in blood pressure and norepinephrine excretion, along with polydipsia and polyuria. The pressor effect of central Ang II was completely blocked in synhACE2 +/+ mice. Polydipsia, norepinephrine excretion, and markers of oxidative stress in response to central Ang II were also reduced in synhACE2 +/+ mice. The MasR (Mas receptor) agonist Ang 1–7 and blocker A779 had no effects on blood pressure. synhACE2 +/+ mice showed enhanced expression of Nrf2 in the rostral ventrolateral medulla which was blunted following Ang II infusion. Ang II evoked nuclear translocation of Nrf2 in cultured Neuro 2A (N2A) cells. In synhACE2 −/− mice, the central Ang II pressor response was attenuated by simultaneous intracerebroventricular infusion of the Nrf2 activator sulforaphane; blood pressure was enhanced by knockdown of Nrf2 in the rostral ventrolateral medulla in Nrf2 floxed (Nrf2 f/f ) mice. These data suggest that the hypertensive effects of intracerebroventricular Ang II are attenuated by selective overexpression of brain synhACE2 and may be mediated by Nrf2-upregulated antioxidant enzymes in the rostral ventrolateral medulla.

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 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation

2020 ◽  
Vol 41 (41) ◽  
pp. 4037-4046 ◽  
Author(s):  
Lars Wallentin ◽  
Johan Lindbäck ◽  
Niclas Eriksson ◽  
Ziad Hijazi ◽  
John W Eikelboom ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Angiotensin Converting Enzyme ◽  
Association Studies ◽  
Cell Surface Receptor ◽  
Genome Wide Association Studies ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Cellular Expression ◽  
Male Sex

Abstract Aims The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability. Methods and results Plasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level. Conclusions Male sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.

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