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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (188)

ProteinN (188)

ORF3a (14)

ProteinE (13)

ProteinM (13)


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SARS-CoV-2 Proteins
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    Interactions between SARS-CoV-2 N-protein PROTEIN and α-synuclein accelerate amyloid formation

    Authors: Slav Semerdzhiev; Mohammad Amin Abolghassemi Fakhree; Ine Segers-Nolten; Christian Blum; Mireille M.A.E. Claessens

    doi:10.1101/2021.04.12.439549 Date: 2021-04-12 Source: bioRxiv

    First cases that point at a correlation between SARS-CoV-2 infections MESHD and the development of Parkinson's disease MESHD have been reported. Currently it is unclear if there also is a direct causal link between these diseases. To obtain first insights into a possible molecular relation between viral infections and the aggregation of -synuclein protein into amyloid fibrils characteristic for Parkinson's disease MESHD, we investigated the effect of the presence of SARS-CoV-2 proteins on synuclein aggregation. We show, in test tube experiments, that SARS-CoV-2 S-protein PROTEIN has no effect on -synuclein aggregation while SARS-CoV-2 N-protein PROTEIN considerably speeds up the aggregation process. We observe the formation of multi-protein complexes, and eventually amyloid fibrils. Microinjection of N-protein PROTEIN in SHSY-5Y cells disturbed the -synuclein proteostasis MESHD and increased cell death. Our results point toward direct interactions between the N-protein PROTEIN of SARS-CoV-2 and -synuclein as molecular basis for the observed coincidence between SARS-CoV-2 infections and Parkinsonism MESHD.

    Ultrastructural insight into SARS-CoV-2 attachment, entry and budding in human airway epithelium

    Authors: Andreia L Pinto; Ranjit K Rai; Jonathan C Brown; Paul Griffin; James R Edgar; Anand Shah; Aran Singanayagam; Claire Hogg; Wendy S Barclay; Clare E Futter; Thomas Burgoyne

    doi:10.1101/2021.04.10.439279 Date: 2021-04-11 Source: bioRxiv

    Ultrastructural studies of SARS-CoV-2 infected MESHD cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Many studies are limited by the lack of access to appropriate cellular models. As the airway epithelium is the primary site of infection it is essential to study SARS-CoV-2 infection MESHD of these cells. Here, we examined human airway epithelium, grown as highly differentiated air-liquid interface cultures and infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant (Variant of Concern 202012/01) by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Two key SARS-CoV-2 entry molecules, ACE2 HGNC and TMPRSS2 HGNC, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistent with these observations, extracellular virions were frequently seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion at the apical plasma membrane demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein PROTEIN-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein PROTEIN. Profiles strongly suggesting viral budding from the membrane was observed in these compartments and this may explain how virions gain their S glycoprotein PROTEIN containing envelope.

    Bead-assisted SARS-CoV-2 multi-antigen serological test allows effective identification of patients

    Authors: Yaiza Caceres-Martell; Daniel Fernandez-Soto; Carmen Campos-Silva; Eva Maria Garcia-Cuesta; Jose M. Casasnovas; David Navas-Herrera; Alexandra Beneitez-Martinez; Pedro Martinez-Fleta; Arantzazu Alfranca; Francisco Sanchez-Madrid; Gabriela Escudero-Lopez; Carlos Vilches; Ricardo Jara-Acevedo; Hugh T. Reyburn; Jose M. Rodriguez-Frade; Mar Vales-Gomez

    doi:10.1101/2021.04.08.21254348 Date: 2021-04-10 Source: medRxiv

    Many new aspects of COVID-19 MESHD disease, including different clinical manifestations, have been identified during the pandemic. The wide array of symptoms and variation in disease severity after SARS-CoV-2 infection MESHD might be related to heterogeneity in the immune responses of different patients. Here we describe a new method for a simple multi-antigen serological test that generates a full picture of seroconversion in a single reaction. The assay is based on the detection by flow cytometry of multiple immunoglobulin classes (isotypes) specific for four SARS-CoV-2 antigens: the Spike glycoprotein PROTEIN (one of the highly immunogenic proteins), its RBD fragment (the major target for neutralising antibodies), the nucleocapsid protein PROTEIN and the main cysteine-like protease PROTEIN. Until now, most diagnostic serological tests measured antibodies to only one antigen and some patients seemed to not make any antibody response. Our data reveal that while most patients respond against all the viral antigens tested, others show a marked bias to make antibodies against either proteins exposed on the viral particle or those released after cellular infection. Combining all the four antigens and using machine learning techniques, it was possible to clearly discriminate between patients and healthy controls with 100% confidence. Further, combination of antigens and different immunoglobulin isotypes in this multi-antigen assay improved the classification of patients with mild and severe disease. Introduction of this method will facilitate massive screenings of patients to evaluate their immune response. It could also support vaccination campaigns both to select non-immune individuals and to distinguish infected MESHD patients from vaccine responders.

    Improved diagnosis of SARS-CoV-2 by using Nucleoprotein PROTEIN and Spike protein PROTEIN fragment 2 in quantitative dual ELISA tests

    Authors: Carolina De Marco Verissimo; Carol O'Brien; Jesus Lopez Corrales; Amber Dorey; Krystyna Cwiklinski; Richard Lalor; Jack M Doyle; Stephen Field; Claire Masterson; Eduardo Ribes Martinez; Gerry Hughes; Colm Bergin; Kieran Walshe; Bairbre McNicholas; John Laffey; John P Dalton; Colm Kerr; Sean Doyle

    doi:10.1101/2021.04.07.21255024 Date: 2021-04-09 Source: medRxiv

    The novel Coronavirus, SARS-CoV-2, is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and Spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative ELISA assays that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive COVID-19 MESHD cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients that had developed severe disease. As antibody tests complement COVID-19 MESHD diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.

    Single Prime hAd5 Spike (S) + Nucleocapsid (N PROTEIN) Dual Antigen Vaccination of Healthy Volunteers Induces a Ten-Fold Increase in Mean S- and N- T-Cell Responses Equivalent to T-Cell Responses from Patients Previously Infected with SARS-CoV-2

    Authors: Pete Sieling; Thomas King; Raymond Wong; Andy Nguyen; Kamil Wnuk; Elizabeth R Gabitzsch; Adrian Rice; Helty Adisetiyo; Melanie Hermreck; Mohit Verma; Lise Zakin; Annie Shin; Brett Morimoto; Wendy Higashide; Kyle Dinkins; Joseph Balint; Victor Peykov; Justin Taft; Roosheel Patel; Sofija Buta; Marta Martin-Fernandez; Dusan Bogunovic; Patricia Spilman; Lennie Sender; Sandeep Reddy; Philip Robinson; Shahrooz Rabizadeh; Kayvan Niazi; Patrick Soon-Shiong

    doi:10.1101/2021.04.05.21254940 Date: 2021-04-07 Source: medRxiv

    In response to the need for a safe, efficacious vaccine that provides broad immune protection against SARS-CoV-2 infection MESHD, we have developed a dual-antigen COVID-19 MESHD vaccine. The vaccine delivers both the viral spike (S) protein PROTEIN modified to increase cell-surface expression (S-Fusion) and the viral nucleocapsid (N) protein PROTEIN with an Enhanced T-cell Stimulation Domain (N-ETSD) to enhance MHC class I and II presentation and T-cell responses. The vaccine antigens are delivered using a human adenovirus serotype 5 (hAd5) platform with E1, E2b, and E3 regions deleted that has been shown in previous cancer MESHD vaccine studies to be effective in the presence of pre-existing hAd5 immunity. Here, we demonstrate the hAd5 S-Fusion + N-ETSD (hAd5 S + N) vaccine antigens when expressed by dendritic cells (DCs) of previously SARS-CoV-2-infected MESHD patients elicit Th1 HGNC dominant activation of autologous patient T cells, indicating the vaccine antigens have the potential for generating immune responses in patients previously infected MESHD or vaccinated. We further demonstrate that participants in our open-label Phase 1b study of the dual-antigen hAd5 S + N vaccine generate Th1 HGNC dominant S- and N- specific T cells after a single prime subcutaneous injection and that the magnitude of these responses were comparable to those seen for T cells from previously infected patients. We further present our in silico prediction of T-cell epitope HLA binding for both the first-wave SARS-CoV-2 A strain and the K417N, E484K, and N501Y S as well as the T201I N variants that suggests T-cell responses to the hAd5 S + N vaccine will retain efficacy against these variants. These findings that the dual-antigen hAd5 S + N vaccine elicits SARS-CoV-2-relevant T-cell responses and that such cell-mediated protection is likely to be sustained against emerging variants supports the testing of this vaccine as a universal booster that would enhance and broaden existing immune protection conferred by currently approved S-based vaccines.

    Analysis of glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike PROTEIN glycoprotein

    Authors: Shijian Zhang; Eden P. Go; Haitao Ding; Saumya Anang; John C. Kappes; Heather Desaire; Joseph G. Sodroski

    doi:10.1101/2021.04.01.438120 Date: 2021-04-01 Source: bioRxiv

    The SARS-CoV-2 coronavirus, the etiologic agent of COVID-19 MESHD, uses its spike ( S) glycoprotein PROTEIN anchored in the viral membrane to enter host cells. The S glycoprotein PROTEIN is the major target for neutralizing antibodies elicited by natural infection and by vaccines. Approximately 35% of the SARS-CoV-2 S glycoprotein PROTEIN consists of carbohydrate, which can influence virus infectivity and susceptibility to antibody inhibition. We found that virus-like particles produced by coexpression of SARS-CoV-2 S MESHD, M, E and N proteins PROTEIN contained spike glycoproteins PROTEIN that were extensively modified by complex carbohydrates. We used a fucose-selective lectin to enrich the Golgi-resident fraction of a wild-type SARS-CoV-2 S glycoprotein PROTEIN trimer, and determined its glycosylation and disulfide bond profile. Compared with soluble or solubilized S glycoproteins PROTEIN modified to prevent proteolytic cleavage and to retain a prefusion conformation, more of the wild-type S glycoprotein PROTEIN N-linked glycans are processed to complex forms. Even Asn 234, a significant percentage of which is decorated by high-mannose glycans on soluble and virion S trimers, is predominantly modified in the Golgi by processed glycans. Three incompletely occupied sites of O-linked glycosylation were detected. Viruses pseudotyped with natural variants of the serine/threonine residues implicated in O-linked glycosylation were generally infectious and exhibited sensitivity to neutralization by soluble ACE2 HGNC and convalescent antisera comparable to that of the wild-type virus. Unlike other natural cysteine variants, a Cys15Phe (C15F) mutant retained partial, but unstable, infectivity. These findings enhance our understanding of the Golgi processing of the native SARS-CoV-2 S glycoprotein PROTEIN carbohydrates and could assist the design of interventions.

    Characterization of antibody response in asymptomatic and symptomatic SARS-CoV-2 infection MESHD

    Authors: Serena Marchi; Viviani Simonetta; Edmond Remarque; Antonella Ruello; Emilio Bombardieri; Valentina Bollati; Gregorio Milani; Alessandro Manenti; Giulia Lapini; Annunziata Rebuffat; Emanuele Montomoli; Claudia Trombetta

    doi:10.1101/2021.03.29.21254534 Date: 2021-03-31 Source: medRxiv

    SARS-CoV-2 pandemic is causing high morbidity and mortality burden worldwide with unprecedented strain on health care systems. To elucidate the mechanism of infection, protection, or rapid evolution until fatal outcome of the disease we performed a study in hospitalized COVID-19 MESHD patients to investigate the time course of the antibody response in relation to the outcome. In comparison we investigated the time course of the antibody response in SARS-CoV-2 asymptomatic subjects. Study results show that patients produce a strong antibody response to SARS-CoV-2 with high correlation between different viral antigens ( spike protein PROTEIN and nucleoprotein PROTEIN) and among antibody classes (IgA, IgG, and IgM and neutralizing antibodies). The peak is reached by 3 weeks from hospital admission followed by a sharp decrease. No difference was observed in any parameter of the antibody classes, including neutralizing antibodies, between subjects who recovered or with fatal outcome. Only few asymptomatic subjects developed antibodies at detectable levels.

    Serological profiles of pan-coronavirus-specific responses in COVID-19 MESHD patients using a multiplexed electro-chemiluminescence-based testing platform

    Authors: Sidhartha Chaudhury; Jack N Hutter; Jessica S Bolton; Shilpa Hakre; Evelyn Mose; Amy I Wooten; William D O'Connell; Joseph Hudak; Shelly J Krebs; Janice Darden; Jason A Regules; Clinton K Murray; Kevin Mojarrad; Sheila A Peel; Elke S Bergmann-Leitner

    doi:10.1101/2021.03.23.21253460 Date: 2021-03-26 Source: medRxiv

    Serological assessment of SARS-CoV-2 specific responses are an essential tool for determining the prevalence of past SARS-CoV-2 infections MESHD in the population especially when testing occurs after symptoms have developed and limited contact tracing is in place. The goal of our study was to test a new 10-plex electro-chemiluminescence-based assay to measure IgM and IgG responses to the spike proteins PROTEIN from multiple human coronaviruses including SARS-CoV-2, assess the epitope specificity of the SARS-CoV-2 antibody response against full-length spike protein PROTEIN, receptor-binding domain and N-terminal domain of the spike protein PROTEIN, and the nucleocapsid protein PROTEIN. We carried out the assay on samples collected from three sample groups: subjects diagnosed with COVID-19 MESHD from the U.S. Army hospital at Camp Humphreys in Pyeongtaek, South Korea; healthcare administrators from the same hospital but with no reported diagnosis of COVID-19 MESHD; and pre-pandemic samples. We found that the new CoV-specific multiplex assay was highly sensitive allowing plasma samples to be diluted 1:30,000 with a robust signal. The reactivity of IgG responses to SARS-CoV-2 nucleocapsid protein PROTEIN and IgM responses to SARS-CoV-2 spike PROTEIN protein could distinguish COVID-19 MESHD samples from non- COVID-19 MESHD and pre-pandemic samples. The data from the three sample groups also revealed a unique pattern of cross-reactivity between SARS-CoV-2 and SARS-CoV-1, MERS-CoV, and seasonal coronaviruses HKU1 and OC43. Our findings show that the CoV-2 IgM response is highly specific while the CoV-2 IgG response is more cross-reactive across a range of human CoVs and also showed that IgM and IgG responses show distinct patterns of epitope specificity. In summary, this multiplex assay was able to distinguish samples by COVID-19 MESHD status and characterize distinct trends in terms of cross-reactivity and fine-specificity in antibody responses, underscoring its potential value in diagnostic or serosurveillance efforts.

    Multiplex Antibody Analysis of IgM, IgA HGNC and IgG to SARS-CoV-2 in Saliva and Serum from Infected Children and their Close Contacts

    Authors: Carlota Dobano; Selena Alonso; Marta Vidal; Alfons Jimenez; Rocio Rubio; Rebeca Santano; Diana Barrios; Gemma Pons Tomas; Maria Mele Casas; Maria Hernandez Garcia; Monica Girona-Alarcon; Laura Puyol; Natalia Rodrigo Melero; Carlo Carolis; Aleix Garcia-Miquel; Elisenda Bonet-Carne; Joana Claverol; Marta Cubells; Claudia Fortuny; Victoria Fumado; Anna Codina; Quique Bassat; Carmen Munoz-Almagro; Mariona Fernandez de Sevilla; Eduard Gratacos; Luis Izquierdo; Juan Jose Garcia-Garcia; Ruth Aguilar; Iolanda Jordan; Gemma Moncunill

    doi:10.1101/2021.03.22.21254120 Date: 2021-03-26 Source: medRxiv

    COVID-19 MESHD affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of the coronavirus in pediatric populations and guide public health interventions. We evaluated the utility of high-throughput Luminex-based assays applied to saliva samples to quantify IgM, IgA HGNC and IgG antibodies against five SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S) and nucleocapsid (N PROTEIN) antigens in the context of a contacts and infectivity longitudinal MESHD study. We compared the antibody levels obtained in saliva versus serum/plasma samples from a group of children and adults tested weekly by RT-PCR over 35 days and diagnosed as positive (n=58), and a group of children and adults who consistently tested negative over the follow up period (n=61), in the Summer of 2020 in Barcelona, Spain. Antibody levels in saliva samples from individuals with confirmed RT-PCR diagnosis of SARS-CoV-2 infection MESHD were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Higher levels of anti-S IgG were found in asymptomatic individuals that could indicate protection against disease in infected MESHD individuals. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa, and therefore that both measurements are complementary. In addition to serum/plasma, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to better estimate the percentage of individuals who have experienced coronavirus infection MESHD. Saliva antibody detection could allow determining COVID-19 MESHD prevalence in pediatric populations, alternative to bleeding MESHD or nasal swab, and serological diagnosis following vaccination.

    Emergence of N antigen SARS-CoV-2 genetic variants escaping detection of antigenic tests

    Authors: Claudia Del Vecchio; Giuseppina Brancaccio; Alessandra Rosalba Brazzale; Enrico Lavezzo; Francesco Onelia; Elisa Franchin; Laura Manuto; Federico Bianca; Vito Cianci; Annamaria Cattelan; Stefano Toppo; Andrea Crisanti

    doi:10.1101/2021.03.25.21253802 Date: 2021-03-26 Source: medRxiv

    SARS-CoV-2 genetic variants are emerging as a major threat to vaccination efforts worldwide as they may increase virus transmission rate and/or confer the ability to escape vaccine induced immunity with knock on effects on the level of herd immunity and vaccine efficacy respectively. These variants concern the Spike protein PROTEIN, which is encoded by the S gene, involved in virus entry into host cells and the major target of vaccine development. We report here that genetic variants of the N gene PROTEIN can impair our ability to utilize antigenic tests for both diagnosis and mass testing efforts aimed at controlling virus transmission. While conducting a large validation study on the Abbott Panbio COVID-19 MESHD Ag test, we noticed that some swab samples failed to generate a positive result in spite of a high viral load in Rt-PCR assays. Sequencing analysis of viruses showing discordant results in the Rt-PCR and antigen assays revealed the presence of multiple disruptive amino-acid substitutions in the N antigen (the viral protein detected in the antigen test) clustered from position 229 to 374 a region known to contain an immunodominant epitope. A relevant fraction of the variants, undetected by the antigen test, contained the mutations A376T coupled to M241I. Intriguingly we found that virus sequences with this mutation were over-represented in the antigen-test-negative and PCR-positive samples and progressively increased in frequency over time in Veneto, a region of Italy that has aggressively scaled up the utilization of antigen tests, which reached nearly 68% of all the SARS-CoV-2 swab assays performed there. We speculate that mass utilization of antigen assays could create a selection pressure on the target that may favor the spread of undetectable virus variants.

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MeSH Disease
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SARS-CoV-2 Proteins


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