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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (12)


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    Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike PROTEIN protein and the human ACE2 HGNC receptor

    Authors: Chen Chen; Veda Sheeresh Boorla; Deepro Banerjee; Ratul Chowdhury; Victoria S Cavener; Ruth H Nissly; Abhinay Gontu; Nina R Boyle; Kurt Vandegrift; Meera Surendran Nair; Suresh V Kuchipudi; Costas D Maranas

    doi:10.1101/2021.03.24.436885 Date: 2021-03-25 Source: bioRxiv

    The association of the receptor binding domain (RBD) of SARS-CoV-2 viral spike with human angiotensin converting enzyme HGNC ( hACE2 HGNC) represents the first required step for viral entry. Amino acid changes in the RBD have been implicated with increased infectivity and potential for immune evasion. Reliably predicting the effect of amino acid changes in the ability of the RBD to interact more strongly with the hACE2 HGNC receptor can help assess the public health implications and the potential for spillover and adaptation into other animals. Here, we introduce a two-step framework that first relies on 48 independent 4-ns molecular dynamics ( MD MESHD) trajectories of RBD- hACE2 HGNC variants to collect binding energy terms decomposed into Coulombic, covalent, van der Waals, lipophilic, generalized Born electrostatic solvation, hydrogen-bonding, {pi}-{pi} packing and self-contact correction terms. The second step implements a neural network to classify and quantitatively predict binding affinity using the decomposed energy terms as descriptors. The computational base achieves an accuracy of 82.2% in terms of correctly classifying single amino-acid substitution variants of the RBD as worsening or improving binding affinity for hACE2 HGNC and a correlation coefficient r of 0.69 between predicted and experimentally calculated binding affinities. Both metrics are calculated using a 5-fold cross validation test. Our method thus sets up a framework for effectively screening binding affinity change with unknown single and multiple amino-acid changes. This can be a very valuable tool to predict host adaptation and zoonotic spillover of current and future SARS-CoV-2 variants.

    The SARS-CoV-2 receptor angiotensin-converting enzyme 2 ( ACE2 HGNC) in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome MESHD: analysis of high-throughput genetic, epigenetic, and gene expression studies

    Authors: João Malato; Franziska Sotzny; Sandra Bauer; Helma Freitag; André Fonseca; Anna D Grabowska; Luís Graça; Clara Cordeiro; Luís Nacul; Eliana M Lacerda; Jesus Castro Marrero; Carmen Scheibenbogen; Francisco Westermeier; Nuno Sepulveda

    doi:10.1101/2021.03.23.21254175 Date: 2021-03-24 Source: medRxiv

    Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome MESHD ( ME/CFS MESHD) show specific epigenetic and gene expression signatures of the disease. However, it is unknown whether these signatures in ME/CFS MESHD include abnormal levels of the human angiotensin-converting enzyme ACE HGNC and ACE2 HGNC, the latter being the main receptor described for host-cell invasion by SARS-CoV-2. To investigate that, we first reviewed published case-control genome-wide association studies based on single nucleotide polymorphism data, case-control epigenome-wide association studies based on DNA methylation data, and case-control gene expression studies based on microarray data. From these published studies, we did not find any evidence for a difference between patients with ME/CFS MESHD and healthy controls in terms of genetic variation, DNA methylation, and gene expression levels of ACE HGNC and ACE2 HGNC. In line with this evidence, the analysis of a new data set on the ACE HGNC/ ACE2 HGNC gene expression in peripheral blood mononuclear cells did not find any differences between a female cohort of 37 patients and 34 age-matched healthy controls. Future studies should be conducted to extend this investigation to other potential receptors used by SARS-CoV-2. These studies will help researchers and clinicians to better assess the health risk imposed by this virus when infecting patients with this debilitating disease.

    Plasma ACE2 HGNC levels predict outcome of COVID-19 MESHD in hospitalized patients

    Authors: Tue W Kragstrup; Helene S Singh; Ida Grundberg; Ane L L Nielsen; Felice Rivellese; Arnav Mehta; Marcia B Goldberg; Michael Filbin; Per Qvist; Bo Martin Bibby

    doi:10.1101/2021.03.08.21252819 Date: 2021-03-10 Source: medRxiv

    Background Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) binds to angiotensin converting enzyme 2 ( ACE2 HGNC) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 ( COVID-19 MESHD). COVID-19 MESHD is a disease with a very broad spectrum of clinical manifestations, ranging from asymptomatic and subclinical infection to severe hyperinflammatory syndrome MESHD and death MESHD. Methods This study used data from a large longitudinal study of 306 COVID-19 MESHD positive patients and 78 COVID-19 MESHD negative patients (MGH Emergency Department COVID-19 MESHD Cohort with Olink Proteomics). Comprehensive clinical data were collected on this cohort, including 28-day outcomes classified according to the World Health Organization (WHO) COVID-19 MESHD outcomes scale. The samples were run on the Olink Explore 1536 platform which includes measurement of the ACE2 HGNC protein. Findings High baseline levels of ACE2 HGNC in plasma from COVID-19 MESHD patients were associated with worse WHOmax category at 28 days with OR=0.56, 95%-CI: 0.44-0.71 (P < 0.0001). This association was significant in regression models with correction for baseline characteristics, pre-existing medical conditions, and laboratory test results. High levels of ACE2 HGNC in plasma from COVID-19 MESHD patients were also significantly associated with worse WHO category at the time of blood sampling at both day 0, day 3, and day 7 (P = 0.0004, P < 0.0001, and P < 0.0001, respectively). The levels of ACE2 HGNC in plasma from COVID-19 MESHD patients with hypertension MESHD were significantly higher compared to patients without hypertension MESHD (P = 0.0045). The plasma ACE2 HGNC levels were also significantly higher in COVID-19 MESHD patients with pre-existing heart conditions and kidney disease MESHD compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). There was no difference in plasma ACE2 HGNC levels comparing patients with or without pre-existing lung disease MESHD, diabetes MESHD, or immunosuppressive conditions (P = 0.953, P = 0.291, and P = 0.237, respectively). The associations between high plasma levels of ACE2 HGNC and worse WHOmax category during 28 days were more pronounced in COVID-19 MESHD positive patients compared with COVID-19 MESHD negative patients but the difference was not significant in the two-way ANOVA analysis. Interpretation This study suggests that measuring ACE2 HGNC is potentially valuable in predicting COVID-19 MESHD outcomes. Further, ACE2 HGNC levels could be a link between severe COVID-19 MESHD disease and its risk factors, namely hypertension MESHD, pre-existing heart disease MESHD and pre-existing kidney disease MESHD. The design of the data analysis using the Olink platform does not allow assessment of quantitative differences. However, previous studies have described a positive correlation between plasma ACE2 HGNC and ACE1 HGNC activity. This is interesting because ACE1 HGNC (serum ACE HGNC) analysis is a standardized test in most hospital laboratories. Therefore, our study encourages quantitative investigations of both plasma ACE 1 and 2 in COVID-19 MESHD.

    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.

    Role of Ecologic ACE HGNC I/D Polymorphism Data Towards Prediction of COVID-19 MESHD Epidemiology

    Authors: Ali Amar; Abdul Rafay Khan; Madiha Shakoor; Aiysha Abid; Shagufta Khaliq

    doi:10.21203/rs.3.rs-259633/v1 Date: 2021-02-20 Source: ResearchSquare

    COVID-19 MESHD displays marked variability in the clinical course as well as regional epidemiology. Abnormalities in RAAS system especially stemming from genetic variability in ACE HGNC and ACE2 HGNC expression (including ACE HGNC I/D polymorphism) have been proposed to explain underlying pathogenesis and variability in SARS-CoV-2 infection MESHD. In a meta-regression data set of 30 countries, we found significant associations of ACE HGNC I/D ratio and COVID-19 MESHD prevalence, deaths MESHD and recovery rate but not when adjusted for possible confounders. This ecological study suggests potential of ACE HGNC I/D data as predictive biomarker COVID-19 MESHD risk and severity in a population specific manner, subject to validation in large genetic epidemiological and functional studies.    

    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. 

    Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2

    Authors: Gard Nelson; Oleksandr Buzko; Aaron Bassett; Patricia R Spilman; Kayvan Niazi; Shahrooz Rabizadeh; Patrick Soon-Shiong; YuFei He; Guang Liu; Xiaohan Han; Hao Wen; Yong Liu; Yifan Chen; Haoyu Wang; Jing Li; Zhongyi Su; Du Chen; Yiting Wang; Xinyang Li; Zeqian Yang; Jie Wang; Min Li; Tiecheng Wang; Ying Wang; Yubo Fan; Hui Wang; Jing Zhang

    doi:10.1101/2020.12.11.422055 Date: 2020-12-12 Source: bioRxiv

    The Receptor Binding Domain (RBD) of the SARS-CoV-2 surface spike (S) protein PROTEIN interacts with host angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) to gain entry to host cells and initiate infection1-3. Detailed, accurate understanding of key interactions between S RBD and ACE2 HGNC provides critical information that may be leveraged in the development of strategies for the prevention and treatment of COVID-19 MESHD. Utilizing the published sequences and cryo-EM structures of both the viral S RBD and ACE HGNC24,5, we performed in silico molecular dynamics ( MD MESHD) simulations of free S RBD and of its interaction with ACE2 HGNC over the exceptionally long durations of 2.9 and 2 milliseconds, respectively, to elucidate the nature and relative affinity of S RBD surface residues for the ACE2 HGNC binding region. Our findings reveal that free S RBD has assumed an optimized ACE2 HGNC binding-ready conformation, incurring little entropic penalty for binding, an evolutionary adaptation that contributes to its high affinity for the receptor6. We further identified high probability molecular binding interactions that inform both vaccine design and therapeutic development, which may include recombinant ACE2 HGNC-based spike decoys7 and/or allosteric S RBD- ACE2 HGNC binding inhibitors8,9 to prevent or arrest infection MESHD and thus disease.

    Sustained Dysregulation of the Plasma Renin-angiotensin System in Acute COVID-19 MESHD

    Authors: Kevin Burns; Matthew Cheng; Todd Lee; Allison McGeer; David Sweet; Karen Tran; Terry Lee; Srinivas Murthy; John Boyd; Joel Singer; Keith Walley; David Patrick; Francois Lamontagne; John Marshall; Greg Haljan; Robert Fowler; Brent Winston; James Russell

    doi:10.21203/rs.3.rs-125380/v1 Date: 2020-12-09 Source: ResearchSquare

    SARS-CoV-2 enters cells by binding to angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), and COVID-19 MESHD infection may therefore induce changes in the renin-angiotensin system (RAS). To determine the effects of COVID-19 MESHD on plasma RAS components, we measured plasma ACE HGNC, ACE2 HGNC, and angiotensins I, (1-7), and II in 46 adults with COVID-19 MESHD at hospital admission and on days 2, 4, 7 and 14, compared to 50 blood donors (controls). We compared survivors vs. non-survivors, males vs. females, ventilated vs. not ventilated, and angiotensin receptor blocker (ARB) and angiotensin-converting enzyme ( ACE HGNC) inhibitor-exposed vs. not exposed. At admission, COVID-19 MESHD patients had higher plasma levels of ACE HGNC (p=0.012), ACE2 HGNC (p=0.001) and angiotensin-(1-7) (p<0.001) than controls. Plasma ACE HGNC and ACE2 HGNC remained elevated for 14 days in COVID-19 MESHD patients, while plasma angiotensin-(1-7) decreased after 7 days. In adjusted analyses, plasma ACE HGNC was higher in males vs. females (p=0.042), and plasma angiotensin I HGNC was significantly lower in ventilated vs. non-ventilated patients (p=0.001). In summary, plasma ACE HGNC and ACE2 HGNC are increased for at least 14 days in patients with COVID-19 MESHD infection. Angiotensin-(1-7) levels are also elevated, but decline after 7 days. The results indicate dysregulation of the RAS with COVID-19 MESHD, with increased circulating ACE2 HGNC throughout the course of infection.Clinical Trial Registration: https://clinicaltrials.gov/ Unique Identifier: NCT04510623

    ACE2 HGNC Nascence, Trafficking and SARS-CoV-2 Pathogenesis: The Saga Continues

    Authors: Sally Badawi; Bassam Ali

    id:10.20944/preprints202011.0673.v1 Date: 2020-11-26 Source: Preprints.org

    With the emergence of the novel corona virus SARS-CoV-2 since December 2019, more than 43 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases leading to over 1 million deaths globally. Despite the collaborative and concerted research efforts that has been made, no effective treatment for COVID-19 MESHD (corona virus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) as an initial mediator for viral attachment and host cell invasion. ACE2 HGNC is widely distributed in human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 HGNC represents a promising therapy for tackling COVID-19 MESHD. In this context, most ACE2 HGNC–based therapeutic strategies have aimed to achieve this through the use of angiotensin converting enzyme HGNC ( ACE HGNC) inhibitors or neutralizing the virus by exogenous administration of ACE2 HGNC. However, through this review, we present another perspective focusing on the subcellular localization and trafficking of ACE2 HGNC. Membrane targeting of ACE2 HGNC, shedding and its cellular trafficking pathways including internalization are not well elucidated. Therefore, hereby we present an overview on the fate of newly synthesized ACE2 HGNC, its post translational modifications, what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 HGNC missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections MESHD. Extensive understanding of these processes is necessary to evaluate the potential use of ACE2 HGNC as a credible therapeutic target.

    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.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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