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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (550)

ProteinS (188)

ComplexRdRp (33)

ProteinE (33)

ORF1ab (27)


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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.

    Antibody response to SARS-CoV-2 mRNA vaccines in pregnant women and their neonates

    Authors: Malavika Prabhu; Elisabeth A Murphy; Ashley C Sukhu; Jim Yee; Sunidhi Singh; Dorothy Eng; Zhen Zhao; Laura E Riley; Yawei Jenny Yang

    doi:10.1101/2021.04.05.438524 Date: 2021-04-06 Source: bioRxiv

    Pregnant women were excluded from initial clinical trials for COVID-19 MESHD vaccines1-2, thus the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies are just beginning to be studied4-5. Methods: Between January 28 and March 31, 2021, we studied 122 pregnant women and their neonates at time of birth. All women had received one or both doses of a messenger RNA (mRNA)-based COVID-19 MESHD vaccine. Fifty-five women received only one dose of the vaccine and 67 women received both doses of the vaccine by time of giving birth. Eighty-five women received the Pfizer-BioNTech vaccine, while 37 women received the Moderna vaccine. All women tested negative for SARS-CoV-2 infection MESHD using reverse-transcriptase PCR on nasopharyngeal swabs, and none reported any COVID-19 MESHD symptoms at the time of admission for birth. Semi-quantitative testing for antibodies against S-Receptor Binding Domain (RBD) (ET HealthCare)3 was performed on sera of maternal peripheral blood and neonatal cord blood at the time of delivery to identify antibodies mounted against the vaccine. All women tested negative for antibodies against the Nucleocapsid Protein PROTEIN (NP) antigen (Roche Diagnostics EUA) to ensure that the antibodies detected were not produced in response to past SARS-CoV-2 infection MESHD. Relationship between IgG antibody levels over time was studied using ANOVA with Tukey posthoc. Relationship between maternal and neonatal IgG levels was studied using Pearson correlation analysis and linear regression on log2-scaled serological values. Relationship between IgG placental transfer ratio (neonatal/maternal) vs. time was studied using Pearson correlation analysis and linear regression on log2-scaled serological values and days. Serology levels represented as log2+1. Statistical analysis was performed using R 3.6.3, RStudio 1.1.463. The study was approved by the Weill Cornell Medicine institutional review board. Results: Pregnant women vaccinated with mRNA-based COVID-19 MESHD vaccines during pregnancy and tested at time of birth had detectable immunoglobulin (Ig)G and IgM response. Eighty-seven women tested at birth produced only an IgG response, and 19 women produced both an IgM and IgG response. Sixteen women tested at birth had no detectable antibody response, and they were all within four weeks after vaccination dose 1 (Figure 1A). There was an increase over time in the number of women that mounted an antibody response, as well as the number of women that demonstrated passive immunity to their neonates (Figure 1A). All women and their neonates, except for one neonate, had detectable IgG antibodies by 4 weeks after maternal first dose of vaccination (Figure 1A). 43.6% (24/55) of neonates born to women that received only one vaccine dose had detectable IgG, while 98.5% (65/67) of neonates born to women that received both vaccine doses had detectable IgG. The IgG levels in pregnant women increased weekly from two weeks after first vaccine dose (p=0.0047;0.019), as well as between the first and second weeks after the second vaccine dose (p=2e-07) (Figure 1B). Maternal IgG levels were linearly associated with neonatal IgG levels (R=0.89, p<2.2e-16) (Figure 2A). Placental transfer ratio correlated with the weeks that elapsed since maternal second dose of vaccine (R=0.8, p=2.6e-15) (Figure 2B). Discussion: mRNA-based COVID-19 MESHD vaccines in pregnant women lead to maternal antibody production as early as 5 days after the first vaccination dose, and passive immunity to the neonate as early as 16 days after the first vaccination dose. The increasing levels of maternal IgG over time, and the increasing placental IgG transfer ratio over time suggest that timing between vaccination and birth may be an important factor to consider in the vaccination strategies of pregnant women. Further studies are needed to understand the factors that influence transplacental transfer of IgG antibody, as well as the protective nature of these antibodies.

    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.

    Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes

    Authors: Xianwu Pang; Pu Li; Lifeng Zhang; Lusheng Que; Min Dong; Qihui Wang; Yinfeng Wei; Bo Xie; Xing Xie; Lanxiang Li; Chunyue Yin; Liuchun Wei; Qingniao Zhou; Yingfang Li; Lei Yu; Weidong Li; Zengnan Mo; Jing Leng; Yanling Hu

    doi:10.1101/2021.03.31.437666 Date: 2021-03-31 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the cause of the ongoing coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a PROTEIN protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 HGNC structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein PROTEIN with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR HGNC and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

    Assessment of serological assays for identifying high titer convalescent plasma

    Authors: Christopher W. Farnsworth; Brett Case; Karl Hock; Rita E Chen; Jane O'Halloran; Rachel Presti; Charles William Goss; Adriana M Rauseo; Ali Ellebedy; Elitza S Theel; Michael Diamond; Jeffrey P Henderson

    doi:10.1101/2021.03.26.21254427 Date: 2021-03-28 Source: medRxiv

    The COVID-19 pandemic MESHD has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose-response data using the Ortho VITROS IgG assay. The proliferation of SARS-CoV-2 serological assays and non-uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between commercially available serological tests (Ortho, Abbott, Roche), a spike ELISA, and a virus neutralization assay using convalescent plasma from a cohort of 79 donors from April 2020. Relationships relative to FDA-approved cutoffs under the CCP EUA were identified by linear regression and receiver operator characteristic curves. Relative to the Ortho VITROS assay, the r2 of the Abbott, Roche, the anti-Spike ELISA and the neutralizing assay were 0.58, 0.5, 0.82, and 0.44, respectively. The best correlative index for establishing high-titer units was 3.82 S/C for the Abbott, 10.89 COI for the Roche, 1:1,202 for the anti-Spike ELISA, and 1:200 by the neutralization assay. The overall agreement using derived cutoffs compared to the CCP EUA Ortho VITROS cutoff of 9.5 was 92.4% for Abbott, 84.8% for Roche, 87.3% for the anti-S ELISA and 78.5% for the neutralization assay. Assays based on antibodies against the nucleoprotein PROTEIN (Roche, Abbott) and neutralizing antibody tests were positively associated with the Ortho assay, although their ability to distinguish FDA high-titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID-19 pandemic MESHD.

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MeSH Disease
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SARS-CoV-2 Proteins


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