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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (15)

NSP5 (2)

ProteinN (1)

ProteinE (1)

ORF1ab (1)


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SARS-CoV-2 Proteins
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    Live imaging of SARS-CoV-2 infection MESHD in mice reveals neutralizing antibodies require Fc function for optimal efficacy

    Authors: Irfan Ullah; Jeremie Prevost; Mark S. Ladinsky; Helen Stone; Maolin Lu; Sai Priya Anand; Guillaume Beaudoin-Bussieres; Mehdi Benlarbi; Shilei Ding; Romain Gasser; Corby Fink; Yaozong Chen; Alexandra Tauzin; Guillaume Goyette; Catherine Bourassa; Halima Medjahed; Matthias Mack; Kunho Chung; Craig B Wilen; Gregory A Dekaban; Jimmy D Dikeakos; Emily A Bruce; Daniel E Kaufmann; Leonidas Stamatatos; Andrew McGuire; Jonathan Richard; Marzena Pazgier; Pamela Bjorkman; Walther Mothes; Andres Finzi; Priti Kumar; Pradeep D Uchil

    doi:10.1101/2021.03.22.436337 Date: 2021-03-22 Source: bioRxiv

    Neutralizing antibodies (NAbs) are effective in treating COVID-19 MESHD but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18- hACE2 HGNC mice intranasally infected with SARS-CoV-2-nanoluciferase. We visualized sequential spread of virus from the nasal cavity to the lungs followed by systemic spread to various organs including the brain, culminating in death MESHD. Highly potent NAbs from a COVID-19 MESHD convalescent subject prevented, and also effectively resolved, established infection when administered within three days of infection. In addition to direct neutralization, in vivo efficacy required Fc effector functions of NAbs, with contributions from monocytes, neutrophils and natural killer cells, to dampen inflammatory responses and limit immunopathology. Thus, our study highlights the requirement of both Fab and Fc effector functions for an optimal in vivo efficacy afforded by NAbs against SARS-CoV-2.

    3D genomic capture of regulatory immuno-genetic profiles in COVID-19 MESHD patients for prognosis of severe COVID disease outcome MESHD

    Authors: Ewan Hunter; Christina Koutsothanasi; Adam Wilson; Francisco Coroado Santos; Matthew Salter; Ryan Powell; Ann Dring; Paulina Brajer; Benedict Egan; Jurjen Westra; Aroul Ramadass; William Messner; Amanda Brunton; Zoe Lyski; Rama Vancheeswaran; Andrew Barlow; Dmitri Pchejetski; Alexandre Akoulitchev

    doi:10.1101/2021.03.14.435295 Date: 2021-03-16 Source: bioRxiv

    Human infection with the SARS-CoV-2 virus leads to coronavirus disease MESHD ( COVID-19 MESHD). A striking characteristic of COVID-19 MESHD infection in humans is the highly variable host response and the diverse clinical outcomes, ranging from clinically asymptomatic to severe immune reactions leading to hospitalization and death MESHD. Here we used a 3D genomic approach to analyse blood samples at the time of COVID diagnosis, from a global cohort of 80 COVID-19 MESHD patients, with different degrees of clinical disease outcomes. Using 3D whole genome EpiSwitch(R) arrays to generate over 1 million data points per patient, we identified a distinct and measurable set of differences in genomic organization at immune-related loci that demonstrated prognostic power at baseline to stratify patients with mild forms of illness and those with severe forms that required hospitalization and intensive care unit (ICU) support. Further analysis revealed both well established and new COVID-related dysregulated pathways and loci, including innate and adaptive immunity; ACE2 HGNC; olfactory, G{beta}{psi}, Ca2+ and nitric oxide (NO) signalling; prostaglandin E2 (PGE2), the acute inflammatory cytokine CCL3 HGNC, and the T-cell derived chemotactic cytokine CCL5 HGNC. We identified potential therapeutic agents for mitigation of severe disease outcome, with several already being tested independently, including mTOR HGNC inhibitors (rapamycin and tacrolimus) and general immunosuppressants (dexamethasone and hydrocortisone). Machine learning algorithms based on established EpiSwitch(R) methodology further identified a subset of 3D genomic changes that could be used as prognostic molecular biomarker leads for the development of a COVID-19 MESHD disease severity test.

    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.

    Pyroptosis of syncytia formed by fusion of SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD and ACE2 HGNC expressing cells

    Authors: Huabin Ma; Zhoujie Zhu; Huaipeng Lin; Shanshan Wang; Peipei Zhang; Yanguo Li; Long Li; Jinling Wang; Yufen Zhao; Jiahuai Han

    doi:10.1101/2021.02.25.432853 Date: 2021-02-25 Source: bioRxiv

    SARS-Cov-2 infected cells fused with the ACE2 HGNC-positive neighboring cells forming syncytia. However, the effect of syncytia in disease development is largely unknown. We established an in vitro cell-cell fusion system and used it to mimic the fusion of SARS-CoV-2 infected MESHD cells with ACE2 HGNC-expressing cells to form syncytia. We found that Caspase-9 HGNC was activated after syncytia formation, and Caspase-3/7 was activated downstream of Caspase-9 HGNC, but it triggered GSDME-dependent pyroptosis rather than apoptosis. What is more, single cell RNA-sequencing data showed that both ACE2 HGNC and GSDME were expression in alveolar type MESHD 2 cells in human lung. We propose that pyroptosis is the fate of syncytia formed by SARS-CoV-2 infected host MESHD cells and ACE2 HGNC-positive cells, which indicated that lytic death of syncytia MESHD may contribute to the excessive inflammatory responses in severe COVID-19 MESHD patients.

    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.    

    Potent Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) by photosensitizers

    Authors: Shujuan Yu; Gaohui Sun; Yaqun Sui; Hanlin Li; Ning Zhang; Yuhai Bi; George Gao; Longguang Jiang; Peng Xu; Cai Yuan; Yang Yang; Mingdong Huang

    doi:10.21203/rs.3.rs-152985/v1 Date: 2021-01-22 Source: ResearchSquare

    The pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has exploded since December 2019, and causes more than 2 million death MESHD with more than 95 million people infected as of Jan. 21th, 2021 globally1,2. Angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), expressed in the lungs, arteries, heart, kidney, intestines, and nasal epithelium3, has been shown to be the primary entry point targeted by the surface spike protein PROTEIN of SARS-CoV-2. Currently, no proven antiviral treatment for SARS-CoV-2 infection MESHD is available. In this study, we screened a number of photosensitizers for photodynamic viral inactivation, and found compounds pentalysine β-carbonylphthalocyanine zinc (ZnPc5K) and chlorin e6 (ce6) potently inhibited the viral infection and replication in vitro with half-maximal effective concentrations (EC50) values at nanomolar level. Such viral inactivation strategy is implementable, and has unique advantages, including resistance to virus mutations, affordability compared to the monoclonal antibodies, and lack of long-term toxicity MESHD.

    The SARS-CoV-2 spike PROTEIN protein disrupts the cooperative function of human cardiac pericytes - endothelial cells through CD147 HGNC receptor-mediated signalling: a potential non-infective mechanism of COVID-19 MESHD microvascular disease

    Authors: Elisa Avolio; Monica Gamez; Kapil Gupta; Rebecca Foster; Imre Berger; Massimo Caputo; Andrew D. Davidson; Darryl Hill; Paolo Madeddu; Shawn A Abbasi; Whitney Pickens; Katia George; Daniel R Boutz; Dalton M Towers; Jonathan R McDaniel; Daniel Billick; Jule Goike; Lori Rowe; Dhwani Batra; Jan Pohl; Justin Lee; Shivaprakash Gangappa; Suryaprakash Sambhara; Michelle Gadush; Nianshuang Wang; Maria D Person; Brent L Iverson; Jimmy D Gollihar; John Dye; Andrew Herbert; Ralph S Baric; Jason S McLellan; George Georgiou; Jason J Lavinder; Gregory C Ippolito; Fergus Gleeson; Yper Hall; Simon G. P. Funnell; Sally Sharpe; Francisco Javier Salguero; Andrew R Gorringe; Miles Carroll

    doi:10.1101/2020.12.21.423721 Date: 2020-12-21 Source: bioRxiv

    Background: Severe coronavirus disease 2019 MESHD ( COVID-19 MESHD) manifests as a life-threatening microvascular syndrome MESHD. The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) uses primarily the capsid spike (S) protein PROTEIN to engage with its receptors and infect host cells. To date, it is still not known if the S protein PROTEIN alone, without the other viral elements, is able to trigger vascular cell signalling and provoke cell dysfunction. Methods: We investigated the effects of the recombinant, stabilised S protein PROTEIN on primary human cardiac pericytes (PCs) signalling and function. Endpoints included cell viability, proliferation, migration, cooperation with endothelial cells (ECs) in angiogenesis assays, and release of pro-inflammatory cytokines. Adopting a blocking strategy against the S protein PROTEIN receptors ACE2 HGNC and CD147 HGNC, we explored which receptor mediates the S protein PROTEIN signalling in PCs. Findings: We show, for the first time, that the recombinant S protein PROTEIN alone elicits functional alterations in cardiac PCs. This was documented as: (1) increased migration, (2) reduced ability to support EC network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm; and (4) production of pro-apoptotic factors responsible for EC death MESHD. Furthermore, the S protein PROTEIN stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 HGNC (ERK1/2) through the CD147 HGNC receptor, but not ACE2 HGNC, in cardiac PCs MESHD. Accordingly, the neutralization of CD147 HGNC, using a blocking antibody, prevented the activation of ERK1/2 and partially rescued the PC function in the presence of the S protein PROTEIN. Interpretation: Our findings suggest the new, intriguing hypothesis that the S protein PROTEIN may elicit vascular cell dysfunction MESHD, potentially amplifying, or perpetuating, the damage caused by the whole coronavirus. This mechanism may have clinical and therapeutic implication.

    pH and Receptor Induced Confirmational Changes- Implications Towards S1 Dissociation of SARS-CoV2 Spike Glycoprotein PROTEIN

    Authors: Jesu E. Castin; Daniel A. Gideon; Karthik S Sudarsha; Sherlin A Rosita; Imre Berger; Massimo Caputo; Andrew D. Davidson; Darryl Hill; Paolo Madeddu; Shawn A Abbasi; Whitney Pickens; Katia George; Daniel R Boutz; Dalton M Towers; Jonathan R McDaniel; Daniel Billick; Jule Goike; Lori Rowe; Dhwani Batra; Jan Pohl; Justin Lee; Shivaprakash Gangappa; Suryaprakash Sambhara; Michelle Gadush; Nianshuang Wang; Maria D Person; Brent L Iverson; Jimmy D Gollihar; John Dye; Andrew Herbert; Ralph S Baric; Jason S McLellan; George Georgiou; Jason J Lavinder; Gregory C Ippolito; Fergus Gleeson; Yper Hall; Simon G. P. Funnell; Sally Sharpe; Francisco Javier Salguero; Andrew R Gorringe; Miles Carroll

    doi:10.1101/2020.12.21.410357 Date: 2020-12-21 Source: bioRxiv

    Viruses, being obligate intracellular parasites, must first attach themselves and gain entry into host cells. Viral fusion machinery is the central player in the viral attachment process in almost every viral disease. Viruses have incorporated an array of efficient fusion proteins on their surfaces to bind efficiently to host cell receptors. They make use of the host proteolytic enzymes to rearrange their surface protein(s PROTEIN) into the form which facilitates their binding to host-cell membrane proteins and subsequently, fusion. This stage of viral entry is very critical and has many therapeutic implications. The current global pandemic of COVID-19 MESHD has sparked severe health crisis and economic shutdowns. SARS-CoV2, the etiological agent of the disease has led to millions of deaths MESHD and brought the scientific community together in an attempt to understand the mechanisms of SARS-CoV2 pathogenesis and mortality. Like other viral fusion machinery, CoV2 spike ( S) glycoprotein PROTEIN- 'The Demogorgon' poses the same questions about viral-host cell fusion. The intermediate stages of S protein PROTEIN-mediated viral fusion are unclear owing to the lack of structural insights and concrete biochemical evidence. The mechanism of conformational transition is still unclear. S protein PROTEIN binding and fusion with host cell receptors, Eg., angiotensin-converting enzyme-2 ( ACE2 HGNC) is accompanied by cleavage of S1/S2 subunits. To track the key events of viral-host cell fusion, we have identified (in silico) that low pH-induced conformational change and ACE-2 HGNC binding events promote S1 dissociation. Deciphering key mechanistic insights of SARS-CoV2 fusion will further our understanding of other class- I fusion proteins.

    IMPACT OF A SARS-COV-2 INFECTION MESHD IN PATIENTS WITH CELIAC DISEASE

    Authors: Luca Elli; Federica Facciotti; Vincenza Lombardo; Alice Scricciolo; David S Sanders; Valentina Vaira; Donatella Barisani; Maurizio Vecchi; Andrea Costantino; Lucia Scaramella; Bernardo Dell'Osso; Luisa Doneda; Leda Roncoroni

    doi:10.1101/2020.12.15.20248039 Date: 2020-12-16 Source: medRxiv

    Objective. The SARS-CoV-2 pandemic has spread across the world causing a dramatic number of infections and deaths MESHD. No data are available about the effects of an infection in patients affected by celiac disease ( CD MESHD) in terms of the development of related symptoms and antibodies. We aimed to investigate the impact of the SARS-CoV-2 pandemic in celiac patients. Design. During a lockdown, the celiac patients living in the Milan area were contacted and interviewed about the development of COVID-19 MESHD symptoms as well as adherence to an anti-virus lifestyle and a gluten-free diet (GFD). They were also given a stress questionnaire to fill in. The development of anti-SARS-CoV-2 IgG and IgA (anti-RBD and N proteins PROTEIN) and the expression of the duodenal ACE2 HGNC receptor were investigated. When available, duodenal histology, anti-tissue transglutaminase IgA (tTGA), presence of immunologic comorbidities and adherence to the GFD were analysed as possible risk factors. Results. 362 celiac patients have been interviewed and 42 (11%) presented with COVID-19 MESHD symptoms. The presence of symptoms was not influenced by tTGA positivity, presence of duodenal atrophy MESHD or adherence to GFD. 37% of the symptomatic patients presented anti-SARS-CoV-2 immunoglobulins (Ig). Globally, 18% of celiac patients showed anti-SARS-CoV-2 Ig vs 25% of the non-celiac control (p=0.18). The values of anti-RBD IgG/IgA and anti-N IgG did not differ from the non-celiac controls. Celiac patients had a significant lower level of anti-N IgA. The ACE2 HGNC receptor was detected in the non-atrophic duodenal mucosa of celiac patients; atrophy MESHD was associated with a lower expression of the ACE2 HGNC receptor. Conclusion. CD MESHD patients have an anti-SARS-CoV-2 Ig positiveness and profile similar to non-celiac controls, except for anti-N IgA. The main celiac parameters and adherence to the GFD do not influence the development of a different Ig profile.

    SARS-CoV-2 Receptors are Expressed on Human Platelets and the Effect of Aspirin on Clinical Outcomes in COVID-19 MESHD Patients

    Authors: Aditya Sahai; Rohan Bhandari; Milka Koupenova; Jane Freedman; Mathew Godwin; Thomas McIntyre; Mina Chung; Jean-Pierre Iskandar; Hayaan Kamran; Anu Aggarwal; Ankur Kalra; John Bartholomew; Keith McCrae; Ayman Elbadawi; Lars Svensson; Samir Kapadia; Essa Hariri; Scott Cameron

    doi:10.21203/rs.3.rs-119031/v1 Date: 2020-11-30 Source: ResearchSquare

    Coronavirus disease-2019 ( COVID-19 MESHD) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic MESHD events. However, the role of platelets in the elevated observed thrombotic MESHD risk in COVID-19 MESHD and utility of anti-platelet agents in attenuating thrombosis MESHD is unknown. We aimed to determine if human platelets express the known SARS-CoV-2 receptor-protease axis on their cell surface and assess whether the anti-platelet effect of aspirin may mitigate risk of myocardial infarction MESHD ( MI MESHD), cerebrovascular accident MESHD ( CVA MESHD), and venous thromboembolism MESHD ( VTE MESHD) in COVID-19 MESHD. Expression of ACE2 HGNC and TMPRSS2 HGNC on human platelets were detected by immunoblotting and confirmed by confocal microscopy. We evaluated 22,072 symptomatic patients tested for COVID-19 MESHD. Propensity-matched analyses were performed to determine if treatment with aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) affected thrombotic MESHD outcomes in COVID-19 MESHD. Neither aspirin nor NSAIDs affected mortality in COVID-19 MESHD. However, both aspirin and NSAID therapies were associated with increased risk of the combined thrombotic endpoint of ( MI MESHD), ( CVA MESHD), and ( VTE MESHD). Thus, while platelets clearly express ACE2 HGNC- TMPRSS2 HGNC receptor-protease axis for SARS-CoV-2 infection MESHD, aspirin does not prevent thrombosis MESHD and death MESHD in COVID-19 MESHD. The mechanisms of thrombosis MESHD in COVID-19 MESHD, therefore, appears distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis MESHD warrants further investigation.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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