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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (151)

ProteinS (69)

ProteinM (9)

ProteinE (9)

ORF1ab (6)


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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.

    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.

    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.

    Detection of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) in a fourplex real-time quantitative reverse transcription-PCR assays.

    Authors: Mathieu Durand; Philippe Thibault; Simon Levesque; Ariane Brault; Alex Carignan; Louis Valiquette; Philippe Martin; Simon Labbe

    doi:10.1101/2021.03.23.21254196 Date: 2021-03-26 Source: medRxiv

    The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections MESHD is required to identify and isolate contagious patients to prevent further transmission of the coronavirus disease 2019 MESHD ( COVID-19 MESHD). In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give SARS-CoV-2 a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N PROTEIN) genes. Furthermore, a newly developed primer-probe set targeted human beta-2 microglobulin HGNC ( B2M HGNC) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected less than or equal to 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of 9 logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to detect multiple viral target sequences containing typical mutations of SARS-CoV-2 variants in a single reaction, allowing quicker detection of circulating relevant variants.

    New detection of SARS-CoV-2 in two cats height months after COVID-19 MESHD outbreak appearance in France

    Authors: Matthieu Fritz; Nicolas Nesi; Solene Denolly; Bertrand Boson; Vincent Legros; Serge G. Rosolen; Alexandra Briend-Marchal; Meriadeg Ar Gouil; Eric M. Leroy

    doi:10.1101/2021.03.24.436830 Date: 2021-03-24 Source: bioRxiv

    Although there are several reports in the literature of SARS-CoV-2 infection MESHD in cats, few SARS-CoV-2 sequences from infected cats have been published. In this report, SARS-CoV-2 infection MESHD was evaluated in two cats by clinical observation, molecular biology (qPCR and NGS), and serology (Microsphere immunoassay and seroneutralization). Following the observation of symptomatic SARS-CoV-2-infection MESHD in two cats, infection status was confirmed by RT-qPCR and, in one cat, serological analysis for antibodies against N-protein PROTEIN and S-protein PROTEIN, as well as neutralizing antibodies. Comparative analysis of five SARS-CoV-2 sequence-fragments obtained from one of the cats showed that this infection was not with one of the three recently emerged variants of SARS-CoV-2. This study provides additional information on the clinical, molecular, and serological aspects of SARS-CoV-2 infection MESHD in cats.

    Clonal dissection of immunodominance and cross-reactivity of the CD4 HGNC+ T cell response to SARS-CoV-2

    Authors: Jun Siong Low; Daniela Vaqueirinho; Federico Mele; Mathilde Foglierini; Michela Perotti; David Jarrossay; Sandra Jovic; Tatiana Terrot; Alessandra Franzetti Pellanda; Maira Biggiogero; Christian Garzoni; Paolo Ferrari; Alessandro Ceschi; Antonio Lanzavecchia; Antonino Cassotta; Federica Sallusto

    doi:10.1101/2021.03.23.436642 Date: 2021-03-23 Source: bioRxiv

    The identification of CD4 HGNC+ T cell epitopes is essential for the design of effective vaccines capable of inducing neutralizing antibodies and long-term immunity. Here we demonstrate in COVID-19 MESHD patients a robust CD4 HGNC+ T cell response to naturally processed SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD and Nucleoprotein PROTEIN, including effector, helper and memory T cells. By characterizing 2,943 Spike-reactive T cell clones, we found that 34% of the clones and 93% of the patients recognized a conserved immunodominant region encompassing residues S346-365 in the RBD and comprising three nested HLA-DR and HLA-DP HGNC restricted epitopes. By using pre- and post- COVID-19 MESHD samples and Spike proteins PROTEIN from alpha and beta coronaviruses, we provide in vivo evidence of cross-reactive T cell responses targeting multiple sites in the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein. The possibility of leveraging immunodominant and cross-reactive T helper epitopes is instrumental for vaccination strategies that can be rapidly adapted to counteract emerging SARS-CoV-2 variants.

    The Dual-Antigen Ad5 COVID-19 MESHD Vaccine Delivered as an Intranasal Plus Subcutaneous Prime Elicits Th1 Dominant T-Cell and Humoral Responses in CD-1 Mice

    Authors: Adrian Rice; Mohit Verma; Annie Shin; Lise Zakin; Peter Sieling; Shiho Tanaka; Joseph Balint; Kyle Dinkins; Helty Adisetiyo; Brett Morimoto; Justin Taft; Roosheel Sandeep Patel; Sofija Buta; Marta Martin-Fernandez; Dusan Bogunovic; Patricia R Spilman; Elizabeth R Gabitzsch; Jeffrey T Safrit; Shahrooz Rabizadeh; Kayvan Niazi; Patrick Soon-Shiong

    doi:10.1101/2021.03.22.436476 Date: 2021-03-23 Source: bioRxiv

    In response to the need for an efficacious, thermally-stable COVID-19 MESHD vaccine that can elicit both humoral and cell-mediated T-cell responses, we have developed a dual-antigen human adenovirus serotype 5 (hAd5) COVID-19 MESHD vaccine in formulations suitable for subcutaneous (SC), intranasal (IN), or oral delivery. The vaccine expresses both the SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S) and nucleocapsid (N) proteins PROTEIN using an hAd5 platform with E1, E2b, and E3 sequences deleted; hAd5(E1-, E2b-, E3-); that is effective even in the presence of hAd5 immunity. In the vaccine, S is modified (S-Fusion) for enhanced cell surface display to elicit humoral responses and N is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal pathway to increase MHC I and II presentation. Initial studies using subcutaneous (SC) prime and SC boost vaccination of CD-1 mice demonstrated that the hAd5 S-Fusion + N-ETSD vaccine elicits T-helper cell 1 (Th1) dominant T-cell and humoral responses to both S and N. We then compared SC to IN prime vaccination with either an SC or IN boost post-SC prime and an IN boost after IN prime. These studies reveal that IN prime/IN boost is as effective at generating Th1 dominant humoral responses to both S and N as the other combinations, but that the SC prime with either an IN or SC boost elicits greater T cell responses. In a third study to assess the power of the two routes of delivery when used together, we used a combined SC plus IN prime with or without a boost and found the combined prime alone to be as effective as the combined prime with either an SC or IN boost in generating both humoral and T-cell responses. The findings here in CD-1 mice demonstrate that combined SC and IN prime-only delivery has the potential to provide broad immunity, including mucosal immunity, against SARS-CoV-2 and supports further testing of this delivery approach in additional animal models and clinical trials.

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MeSH Disease
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SARS-CoV-2 Proteins


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