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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    Soluble angiotensin-converting enzyme 2 HGNC is transiently elevated in COVID-19 MESHD and correlates with specific inflammatory and endothelial markers

    Authors: Annika Lundstrom; Louise Ziegler; Sebastian Havervall; Ann-Sofie Rudberg; Fien Von Meijenfeldt; Ton Lisman; Nigel Mackman; Per Sanden; Charlotte Thalin

    doi:10.1101/2021.03.03.21252841 Date: 2021-03-05 Source: medRxiv

    RationaleAngiotensin-converting enzyme 2 ( ACE2 HGNC) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 HGNC influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is unknown. ObjectiveTo measure circulating ACE2 HGNC and ACE HGNC levels in COVID-19 MESHD patients and investigate association with risk factors, outcome and inflammatory markers. Methods and resultsSoluble ACE2 HGNC (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 MESHD patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand MESHD Von Willebrand HGNC factor ( VWF HGNC), factor VIII ( fVIII HGNC), D-dimer, interleukin 6 ( IL-6 HGNC), tumor necrosis MESHD factor and plasminogen activator inhibitor 1 ( PAI-1 HGNC) had previously been determined. Levels of sACE2 were higher in COVID-19 MESHD patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19 MESHD. sACE 2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes MESHD and patients on RAS-inhibition. sACE was marginally lower during COVID-19 MESHD compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 MESHD correlated with VWF HGNC, fVIII HGNC and D-dimer, while sACE correlated with IL-6 HGNC, TNF HGNC and PAI-1 HGNC. ConclusionssACE2 was transiently elevated in COVID-19 MESHD, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 MESHD differed distinctly in their correlations with markers of inflammation MESHD and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

    Renin HGNC-Angiotensin System Blockade Influences ACE2 HGNC in Human Type II Pneumocytes

    Authors: Mauro G Silva; Nora L Falcoff; Gerardo C Corradi; José Alfie; Rolando F. Seguel; Gabriela Tabaj; Laura Iglesias; Myriam Nuñez; Gabriela R. Guman; Mariela M. Gironacci

    doi:10.21203/rs.3.rs-159733/v2 Date: 2021-01-27 Source: ResearchSquare

    Rationale— Angiotensin converting enzyme (ACE) 2 HGNC and the transmembrane protease serine 2 HGNC ( TMPRSS2 HGNC) are key for cellular entry of the type 2 coronavirus that causes severe acute respiratory syndrome MESHD (SARS-CoV2), the etiological agent of coronavirus-19 disease MESHD ( COVID-19 MESHD). There has been a growing concern that renin HGNC-angiotensin system (RAS) blockade with ACE HGNC inhibitors (ACEIs) or type 1 angiotensin (Ang II) receptor blockers (ARBs) increases ACE2 HGNC expression and then elevate patient susceptibility to SARS-CoV-2.  However, evidence about RAS blockade and ACE2 HGNC in human lung are lacking.Objective– To investigate RAS blockade on ACE2 HGNC and TMPRSS2 HGNC in type II pneumocytes of human lung parenchymal of untreated and ACEI/ARB-treated hypertensive MESHD subjects.Methods and Results– ACE2 HGNC and TMPRSS2 HGNC protein expression were measured by immunohistochemistry. We found that smoking and RAS blockade influence on the percentage of human ACE2 HGNC-expressing type II pneumocytes (p= 0.026). Smokers subjects under RAS blockade treatment exhibited higher percentage of ACE2 HGNC-expressing type II pneumocytes than normotensive ones. Within the ACEI/ARB-treated group, the percentage of ACE2 HGNC-expressing type II pneumocytes was higher in smokers than never smokers. A significant association between ACE2 HGNC immunostaining intensity and smoking on subjects over 60 years old was found (p= 0.05): older smokers exhibited higher ACE2 HGNC protein levels compared to youngers. The percentage of TMPRSS2 HGNC-expressing type II pneumocytes was greater in men than women (p= 0.026) and in subjects under 60 years old (p= 0.040) and trend to be higher in ACEI/ARB-treated subjects than normotensives (p= 0.060). A significant association between TMPRSS2 HGNC immunostaining intensity with smoking and age or with RAS blockade MESHD and age or with RAS blockade MESHD and smoking was observed. Older or smokers subjects under ACEI/ARB treatment exhibited higher TMPRSS2 HGNC protein levels than youngers or never smokers.Conclusions— ACE2 HGNC and TMPRSS2 HGNC are influenced by smoking and ACEI/ARB treatment. These findings help explain the increased susceptibility to COVID-19 MESHD in subjects with treated cardiovascular-related pathologies. 

    Carnosine to Combat Novel Coronavirus (nCoV, COVID-19 MESHD): Molecular Docking and Modeling to Co-Crystallized Host Angiotensin-Converting Enzyme 2 HGNC ( ACE2 HGNC) and Viral Spike Protein PROTEIN

    Authors: Loai M. Saadah; Ghina’a I Abu Deiab; Qosay Al-Balas; Iman A. Basheti

    id:10.20944/preprints202010.0486.v1 Date: 2020-10-23 Source: Preprints.org

    Aims: Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) plays an important role in the entry of coronaviruses into host cells. This paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease MESHD ( COVID-19 MESHD) on the basis of molecular docking and modeling to host ACE2 HGNC co-crystallized with COVID-19 MESHD spike protein PROTEIN. Methods: First, the starting point was ACE2 HGNC inhibitors and their structure-activity relationship ( SAR HGNC). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19 MESHD. In parallel, at all stages, authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2 HGNC. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 HGNC co-crystallized with COVID-19 MESHD spike protein PROTEIN. Results: Carnosine emerged as the best known drug candidate to match ACE2 HGNC inhibitor structure. Preliminary docking was more optimal to ACE2 HGNC than the known typical angiotensin-converting enzyme 1 ( ACE1 HGNC) inhibitor (enalapril) and quite comparable to known or presumed ACE2 HGNC inhibitors. Viral spike protein PROTEIN elements binding to ACE2 HGNC were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the co-crystallized protein structure, carnosine bind with higher affinity to two compared to the known ACE2 HGNC active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 HGNC co-crystallized with COVID-19 MESHD spike protein PROTEIN and hence could offer potential mitigating effect against current COVID-19 pandemic MESHD.

    Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike PROTEIN protein

    Authors: Giuseppe Deganutti; Filippo Prischi; Christopher A. Reynolds

    doi:10.21203/rs.3.rs-64722/v1 Date: 2020-08-24 Source: ResearchSquare

    The recent outbreak of the respiratory syndrome MESHD-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease MESHD ( COVID-19 MESHD). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs approved for other diseases. The first interaction between the virus and the host cell is mediated by the spike protein PROTEIN on the virus surface and the human angiotensin-converting enzyme HGNC ( ACE2 HGNC). Small molecules able to bind the receptor-binding domain (RBD) of the spike protein PROTEIN and disrupt the binding to ACE2 HGNC would offer an important tool for slowing, or even preventing, the infection. Here, we screened 2421 approved small molecules in silico and validated the docking outcomes through extensive molecular dynamics simulations. Out of six drugs characterized as putative RBD binders, the cephalosporin antibiotic cefsulodin was further assessed for its effect on the binding between the RBD and ACE2 HGNC, suggesting the importance of considering the dynamic formation of the heterodimer when judging any potential candidate.

    Repurposing of Approved Drugs with Potential to Interact with SARS-CoV-2 Receptor

    Authors: Abu Sajib

    id:202004.0369/v2 Date: 2020-08-02 Source: Preprints.org

    Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection MESHD. Angiotensin I converting enzyme 2 HGNC ( ACE2 HGNC) is the known receptor of SARS-CoV-2 surface spike glycoprotein PROTEIN for entry into human cells. A recent study reported absent to low expression of ACE2 HGNC in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 HGNC (a homolog of ACE2 HGNC and also known as ACE HGNC) in human lungs compared to very low expression of ACE2 HGNC. In fact, ACE1 HGNC has a wider and more abundant tissue distribution compared to ACE2 HGNC. Although it is not obvious from the primary sequence alignment of ACE1 HGNC and ACE2 HGNC, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2 HGNC) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike PROTEIN protein. Critical amino acids in ACE2 HGNC that mediate interaction with the viral spike protein PROTEIN are present and organized in the same order in the PD of ACE1 HGNC. In silico analysis predicts comparable interaction of SARS-CoV-2 spike PROTEIN protein with ACE1 HGNC and ACE2 HGNC. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 HGNC and/or ACE1 HGNC, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease MESHD ( COVID-19 MESHD).

    Repurposing of Approved Drugs with Potential to Interact with SARS-CoV-2 Receptor

    Authors: Abu Sajib

    id:10.20944/preprints202004.0369.v2 Date: 2020-08-02 Source: Preprints.org

    Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection MESHD. Angiotensin I converting enzyme 2 HGNC ( ACE2 HGNC) is the known receptor of SARS-CoV-2 surface spike glycoprotein PROTEIN for entry into human cells. A recent study reported absent to low expression of ACE2 HGNC in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 HGNC (a homolog of ACE2 HGNC and also known as ACE HGNC) in human lungs compared to very low expression of ACE2 HGNC. In fact, ACE1 HGNC has a wider and more abundant tissue distribution compared to ACE2 HGNC. Although it is not obvious from the primary sequence alignment of ACE1 HGNC and ACE2 HGNC, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2 HGNC) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike PROTEIN protein. Critical amino acids in ACE2 HGNC that mediate interaction with the viral spike protein PROTEIN are present and organized in the same order in the PD of ACE1 HGNC. In silico analysis predicts comparable interaction of SARS-CoV-2 spike PROTEIN protein with ACE1 HGNC and ACE2 HGNC. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 HGNC and/or ACE1 HGNC, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease MESHD ( COVID-19 MESHD).

    Prognostic Significance of COVID-19 MESHD Receptor ACE2 HGNC and Recommendation For Anti-Hypertensive Drug in Renal Cell Carcinoma

    Authors: Kihun Kim; Yeji Ko; Dai Sik Ko; Yun Hak Kim

    doi:10.21203/rs.3.rs-49602/v1 Date: 2020-07-27 Source: ResearchSquare

    Background: Owing to its worldwide spread, the coronavirus disease MESHD ( COVID-19 MESHD) epidemic was declared a pandemic by the World Health Organization on March 11 HGNC, 2020. Angiotensin-converting enzyme 2 ( ACE2 HGNC) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys, and plays an important role in molecular docking of the severe acute respiratory syndrome coronavirus 2. In this study, we aimed to analyze the difference in the survival rate according to ACE2 HGNC expressions in pan- cancer MESHD. Methods: The clinical and genomic data of pan- cancer MESHD patients were accessed from The cancer MESHD Genome Atlas. To identify the prognostic significance of ACE2 HGNC, we used Kaplan-Meier with log-rank test, and the Cox HGNC proportional hazards regression to analyze prognostic significance. Results: In the Kaplan-Meier curve, clear cell renal cell carcinoma MESHD ( ccRCC MESHD), uveal melanoma MESHD, and prostate adenocarcinoma MESHD showed statistically significant. In the Cox HGNC regression, thyroid carcinoma MESHD and glioblastoma multiforme MESHD, and ccRCC MESHD showed significant results. Only ccRCC MESHD had statistically significant, and high ACE2 HGNC expression is related to good prognosis. Conclusions: It is known that ACE HGNC inhibitor, a primary antihypertensive agent, increases ACE2 HGNC expression. Based on these results, we believe that the ACE HGNC inhibitor will be important to increase the lifespan of ccRCC MESHD patients. This study is the first research to offer a recommendation on the use of anti- hypertensive MESHD drugs to ccRCC MESHD patients.

    Type 1 diabetes onset triggered by COVID-19 MESHD

    Authors: Lucien Marchand; Matthieu Pecquet; Cédric Luyton

    doi:10.21203/rs.3.rs-38116/v1 Date: 2020-06-27 Source: ResearchSquare

    The epidemic of coronavirus disease-2019 ( COVID-19 MESHD) is caused by the severe acute respiratory syndrome-coronavirus-2 MESHD (SARS-CoV-2) virus. Some data describing characteristics and prognosis of patients with COVID-19 MESHD and diabetes MESHD are now available, for example for hospitalized patients in the CORONADO study. Potential links between diabetes MESHD and COVID-19 MESHD infection were already described. Indeed Angiotensin-converting-enzyme 2 HGNC ( ACE2 HGNC) has been identified as the receptor for the coronavirus spike protein PROTEIN, and ACE HGNC is expressed on pancreatic beta cells. It was suggested that SARS-CoV2 could induce beta cell damage and new onset diabetes MESHD, but the phenotype of these new cases of diabetes MESHD has not been described.This observation presented in that paper highlights the fact that COVID-19 MESHD infection may also trigger type 1 diabetes MESHD onset. Viral infection MESHD, in particular by enteroviruses but also by coronaviruses, is a well-known environmental trigger for the development of type 1 diabetes MESHD. In the case presented herein, there was a short delay between COVID-19 MESHD infection and diabetes MESHD onset. It remains to determine if the hyperinflammation/cytokine storm described with this infection could accelerate the onset of type 1 diabetes MESHD in genetically susceptible individuals.The relationship between SARS-CoV2 exposition and autoimmune diabetes MESHD development must be further studied, and incidence of type 1 diabetes MESHD will be carefully observed in the next months.

    The Association Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Number of Covid-19 MESHD Confirmed Cases and Deaths in the United States: Geospatial Study

    Authors: Kyle Johnson; Maedeh Khayyat-Kholghi; Blake Johnson; Larisa G Tereshchenko

    doi:10.1101/2020.05.31.20118802 Date: 2020-06-01 Source: medRxiv

    Background: The novel coronavirus SARS-Cov2 uses the angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptor as an entry point to the cell. Cardiovascular disease MESHD ( CVD MESHD) is a risk factor for the novel coronavirus disease MESHD ( Covid-19 MESHD) with poor outcomes. We hypothesized that the rate of ACE HGNC inhibitor (ACEI) and angiotensin receptor blocker (ARB) use is associated with the rate of Covid-19 MESHD confirmed cases and deaths MESHD. Methods: We conducted a geospatial study using publicly available county-level data. The Medicare ACEI and ARB prescription rate was exposure. The Covid-19 MESHD confirmed case and death MESHD rates were outcomes. Spatial autoregression models were adjusted for the percentage of Black residents, children, residents with at least some college degree, median household income, air quality index, CVD MESHD hospitalization rate in Medicare beneficiaries, and CVD death MESHD rate in a total county population. Findings: After adjustment for confounders, the ACEI use rate did not associate with Covid-19 MESHD confirmed case rate (direct county-own effect +0.11 %; 95%CI -0.31 to 0.53; P=0.600, and indirect spillover effect -0.53 %; 95%CI -3.89 to 2.84; P=0.760). The ARB use rate was associated with increased Covid-19 MESHD confirmed case rate (direct county-owned effect +0.12 %; 95%CI 0.05-0.19; P=0.002, and indirect spillover effect -0.33 %; 95%CI -2.11 to 1.44; P=0.714). Sensitivity analysis indicated an absence of significant reverse causality bias for analyses with Covid-19 MESHD confirmed case rate, but not death rate outcome. Interpretation: Our results highlight the safety of ACEI use for patients with clinical indications for ACEI use. However, an increase in ARB use by 1% was associated with a 0.12 % increase in Covid-19 MESHD confirmed cases. The use of ARB, due to known ACE2 HGNC upregulation, may facilitate SARS-CoV-2 entry into target cells and increase infectivity. Cluster-randomized controlled trial is warranted to answer the question of whether the replacement of ARB by ACEI may reduce the Covid-19 MESHD confirmed case rate.

    The Binding Mechanism of Coronavirus Disease 2019 MESHD with Human Angiotensin Converting Enzyme HGNC 2

    Authors: Baliram Lone; Megha Lone

    id:10.20944/preprints202005.0186.v1 Date: 2020-05-11 Source: Preprints.org

    The outbreak across the globe due to coronavirus disease 2019 MESHD ( COVID-19 MESHD) has spread abruptly by infected humans worldwide. The continuous efforts by scientists is on way to understand how pandemic of COVID-19 MESHD resembles and differs from serve acute respiratory syndrome coronavirus (SARS-CoV MESHD) at transcriptomic and genomic level. The SARS-CoV MESHD and COVID-19 MESHD exploits the angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) receptor to gain entry inside the cells.We analyzed the entry COVID-19 MESHD into host cell due to receptor binding domain (RBD) of spike glycoprotein PROTEIN. The proposed simulation data shows similar ternary structures from two viruses shares approximately 80 percent identity in amino acid sequences. Our molecular modeling investigation signifies that angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) has stronger interaction with COVID -19 RBD. The Amino acid phenylaniline F486 LOOP plays vital role due to its penetration into hydrophobic pocket in ACE2 HGNC.The said investigation of S-Glycoprotein PROTEIN RBD of COVID-19 MESHD or SARS-CoV-2 via ACE2 HGNC provides post genome analysis of protein-protein interaction for rapid assessing transmission of infected MESHD patients by deadly CoVID-19 MESHD. The scientific data extracted implies early guidance to control and viral prevention of CoVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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