Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (547)

ProteinS (185)

ComplexRdRp (33)

ProteinE (33)

ORF1ab (27)


SARS-CoV-2 Proteins
    displaying 31 - 40 records in total 547
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    Reducing the Cost of Rapid Antigen Tests through Swab Pooling and Extraction in a Device

    Authors: Tim Berking; Sabrina G Lorenz; Alexander Ulrich; Joachim Greiner; Clemens Richert

    doi:10.1101/2021.03.11.21252969 Date: 2021-03-12 Source: medRxiv

    The COVID-19 pandemic MESHD places a significant stress on the viral testing capabilities of many countries. The value of rapid point-of-care ( PoC HGNC) antigen tests is becoming increasingly clear, but implementing frequent large scale testing is costly. We have developed an inexpensive device for pooling swabs, extracting specimens, and detecting viral antigens with a commercial lateral flow assay detecting the nucleocapsid protein PROTEIN of SARS-CoV-2 as antigen. The holder of the device can be produced locally through 3D printing. The extraction and the elution can be performed with the entire set-up encapsulated in a transparent bag, minimizing the risk of infection for the operator. With 6 swabs holding approx. 0.1 mL specimen each and 0.35 mL extraction buffer, 43+/-6 % (n= 8) of the signal for an individual extraction of a positive control standard was obtained. Image analysis still showed a signal-to-noise ratio of > 7 upon further eight-fold dilution. Our current total cost of materials is below $ 2 per tested person or 20% of our cost for an individual PoC HGNC test. These findings suggest that pooling can make frequent testing more affordable for schools, universities and other institutions, without decreasing sensitivity to an unacceptable level. Further validation of the method is required.

    Evaluation of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 MESHD patients in outbreak on a cruise ship

    Authors: Norihito Kaku; Fumitaka Nishimura; Yui Shigeishi; Rina Tachiki; Hironori Sakai; Daisuke Sasaki; Kenji Ota; Kei Sakamoto; Kosuke Kosai; Hiroo Hasegawa; Koichi Izumikawa; Koya Ariyoshi; Hiroshi Mukae; Jiro Yasuda; Kouichi Morita; Shigeru Konno; Katsunori Yanagihara

    doi:10.1101/2021.03.10.21253064 Date: 2021-03-12 Source: medRxiv

    Background A few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 MESHD ( COVID-19 MESHD) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 MESHD patients. Methods Blood samples were collected from 143 COVID-19 MESHD patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a second SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic MESHD were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins PROTEIN were measured using the enzyme-linked immunosorbent assay to compare false-negative- with positive-result samples. Results Sensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. IgM-, IgG-, and total-antibody positivity rates in the patients with negative results from the second genetic testing were 22.9%, 47.6%, and 72.4%, respectively. All antibody titers, especially those of the IgG antibody against nucleocapsid protein PROTEIN, were significantly lower in blood samples with false-negative results than in those with positive results. Conclusions These findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 MESHD patients than required in the guidelines, and situations in which it is useful are limited.

    SARS-CoV-2 seroassay optimization and performance in a population with high background reactivity in Mali

    Authors: John Woodford; Issaka Sagara; Jennifer Kwan; Amatigue Zeguime; Irfan Zaidi; Oumar Attaher; Mamady Kone; Justin Y.A. Doritchamou; Jonathan Renn; Mahamadoun Maiga; Halimatou Diawara; Maryonne Snow-Smith; Nada Alani; M'Bouye Doucoure; Ivan Kosik; Jaroslav Holly; Jonathan Yewdell; Dominic Esposito; Kaitlyn Sadtler; Alassane Dicko; Patrick E. Duffy

    doi:10.1101/2021.03.08.21252784 Date: 2021-03-12 Source: medRxiv

    Serological tests are an indispensable tool to understand the epidemiology of the SARS-CoV-2 pandemic, particularly in areas where molecular diagnostics are limited. Poor assay performance may hinder the utility of these tests, including high rates of false-positivity previously reported in sub-Saharan Africa. From 312 Malian samples collected prior to 2020, we measured antibodies to the commonly tested SARS-CoV-2 antigens and four other betacoronaviruses by ELISA, and assessed functional cross-reactivity in a subset by SARS-CoV-2 pseudovirus neutralization assay. We then evaluated the performance of an ELISA developed in the US, using two-antigen SARS-CoV-2 spike PROTEIN protein and receptor-binding domain. To optimize test performance, we compared single and two-antigen approaches using existing assay cutoffs and population-specific cutoffs for Malian control samples (positive and negative). Background reactivity to SARS-CoV-2 antigens was common in pre-pandemic samples compared to US controls (43.4% (135/311) for spike protein PROTEIN, 22.8% (71/312) for RBD, and 33.9% (79/233) for nucleocapsid protein PROTEIN). SARS-CoV-2 reactivity correlated weakly with other betacoronavirus reactivity, varied between Malian communities, and increased with age. No pre-pandemic samples demonstrated functional activity. Regardless of the cutoffs applied, specificity improved using a two-antigen approach. Test performance was optimal using a two-antigen assay with population-specific cutoffs derived from ROC curve analysis [Sensitivity: 73.9% (51.6-89.8), Specificity: 99.4% (97.7-99.9)]. In the setting of high background reactivity, such as sub-Saharan Africa, SARS-CoV-2 serological assays need careful qualification is to characterize the epidemiology of disease, prevent unnecessary harm, and allocate resources for targeted control measures.

    Native Hydrophobic Interaction Chromatography Hyphenated to Multi-Angle Light Scattering Detection for In-Process Control of SARS-CoV-2 Nucleocapsid Protein PROTEIN Produced in Escherichia Coli

    Authors: Jelle De Vos; Patricia Pereira Aguilar; Christoph Köppl; Andreas Fischer; Clemens Grünwald-Gruber; Mark Dürkop; Miriam Klausberger; Juergen Mairhofer; Gerald Striedner; Monika Cserjan-Puschmann; Alois Jungbauer; Nico Lingg

    doi:10.26434/chemrxiv.14195318.v1 Date: 2021-03-11 Source: ChemRxiv

    The nucleocapsid protein PROTEIN (NP) of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is critical for several steps of the viral life cycle, and is abundantly expressed during infection, making it an ideal diagnostic target protein. This protein has a strong tendency to dimerization and interaction with nucleic acids. A native hydrophobic interaction chromatography hyphenated to multi-angle light scattering detection (HIC-MALS) method was established for in-process control, in particular, to monitor product fragmentation and multimerization throughout the purification process. High titers of the nucleocapsid protein PROTEIN were expressed in E. coli with a CASPON tag, using a growth-decoupled protein expression system. Purification was accomplished by nuclease treatment of the cell homogenate and a sequence of chromatographic steps. 730 mg purified NP per liter of fermentation could be produced by the optimized process, corresponding to a yield of 77%. The HIC-MALS method was used to demonstrate that the NP product can be produced with a purity of 95%. The molecular mass of the main NP fraction is consistent with dimerized protein as was verified by a complementary native size-exclusion separation (SEC)-MALS analysis. Peptide mapping mass spectrometry and host cell specific enzyme-linked immunosorbent assay confirmed the high product purity, and the presence of a minor endogenous chaperone explained the residual impurities. The HIC-MALS method enables to monitor the purity of the product and simultaneously access its molecular mass.

    Spike vs nucleocapsid SARS-CoV-2 antigen detection: application in nasopharyngeal swab specimens

    Authors: Moria Barlev-Gross; Shay Weiss; Amir Ben-Shmuel; Assa Sittner; Keren Eden; Noam Mazuz; Itai Glinert; Elad Bar-David; Reut Puni; Sharon Amit; Or Kriger; Ofir Schuster; Ron Alcalay; Efi Makdasi; Eyal Epstein; Tal Noy-Porat; Ronit Rosenfeld; Hagit Achdout; Ohad Mazor; Tomer Israely; Haim Levy; Adva Mechaly

    doi:10.1101/2021.03.08.21253148 Date: 2021-03-11 Source: medRxiv

    Public health experts emphasize the need for quick, point-of-care SARS-CoV-2 detection as an effective strategy for controlling virus spread. To this end, many antigen detection devices were developed and commercialized. These devices are mostly based on detecting SARS-CoV-2 nucleocapsid protein PROTEIN. Recently, alerts issued by both the FDA and the CDC raised concerns regarding the devices tendency to exhibit false positive results. In this work we developed a novel alternative spike-based antigen assay, comprised of four high-affinity, specific monoclonal antibodies, directed against different epitopes on the spike S1 subunit PROTEIN. The assay performance was evaluated for COVID-19 MESHD detection from nasopharyngeal swabs, compared to an in-house nucleocapsid-based assay, composed of antibodies directed against the nucleocapsid. Detection of COVID-19 MESHD was carried out in a cohort of 284 qRT-PCR positive and negative nasopharyngeal swab samples. The time resolved fluorescence (TRF) ELISA spike-assay displayed very high specificity (99%) accompanied with a somewhat lower sensitivity (66% for Ct<25 HGNC), compared to the nucleocapsid ELISA assay which was more sensitive (85% for Ct<25 HGNC) while less specific (87% specificity). Despite being out-performed by qRT-PCR, we suggest that there is room for such tests in the clinical setting, as cheap and rapid pre-screening tools. Our results further suggest that when applying antigen detection, one must consider its intended application (sensitivity vs specificity), taking into consideration that the nucleocapsid might not be the optimal target. In this regard, we propose that a combination of both antigens might contribute to the validity of the results.

    Functional Antibodies in COVID-19 MESHD Convalescent Plasma

    Authors: Jonathan D Herman; Chuangqi Wang; Carolin Loos; Hyun ah Yoon; Johanna Rivera; M. Eugenia Dieterle; Denise Haslwanter; Rohit K Jangra; Robert Bortz; Katharine Bar; Boris Julg; Kartik Chandran; Liise-anne Pirofski; Douglas Lauffenburger; Galit Alter

    doi:10.1101/2021.03.08.21253157 Date: 2021-03-11 Source: medRxiv

    In the absence of an effective vaccine or monoclonal therapeutic, transfer of convalescent plasma (CCP) was proposed early in the SARS-CoV-2 pandemic as an easily accessible therapy. However, despite the global excitement around this historically valuable therapeutic approach, results from CCP trials have been mixed and highly debated. Unlike other therapeutic interventions, CCP represents a heterogeneous drug. Each CCP unit is unique and collected from an individual recovered COVID-19 MESHD patient, making the interpretation of therapeutic benefit more complicated. While the prevailing view in the field would suggest that it is administration of neutralizing antibodies via CCP that centrally provides therapeutic benefit to newly infected COVID-19 MESHD patients, many hospitalized COVID-19 MESHD patients already possess neutralizing antibodies. Importantly, the therapeutic benefit of antibodies can extend far beyond their simple ability to bind and block infection MESHD, especially related to their ability to interact with the innate immune system. In our work we deeply profiled the SARS-CoV-2-specific Fc-response in CCP donors, along with the recipients prior to and after CCP transfer, revealing striking SARS-CoV-2 specific Fc-heterogeneity across CCP units and their recipients. However, CCP units possessed more functional antibodies than acute COVID-19 MESHD patients, that shaped the evolution of COVID-19 MESHD patient humoral profiles via distinct immunomodulatory effects that varied by pre-existing SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN (S)-specific IgG titers in the patients. Our analysis identified surprising influence of both S and Nucleocapsid (N PROTEIN) specific antibody functions not only in direct antiviral activity but also in anti-inflammatory effects. These findings offer insights for more comprehensive interpretation of correlates of immunity in ongoing large scale CCP trials and for the design of next generation therapeutic design.

    Serological reconstruction of COVID-19 MESHD epidemics through analysis of antibody kinetics to SARS-CoV-2 proteins MESHD

    Authors: Stephane Pelleau; Tom Woudenberg; Jason Rosado; Francoise Donnadieu; Laura Garcia; Thomas Obadia; Soazic Gardais; Yasmine Elgharbawy; Aurelie Velay; Maria Gonzalez; Jacques-Yves Nizou; Nizar Khelil; Konstantinos Zannis; Charlotte Cockram; Sarah Merkling; Annalisa Meola; Solen Kerneis; Benjamin Terrier; Jerome de Seze; Delphine Planas; Olivier Schwartz; Francois Dejardin; Stephane Petres; Cassandre von Platen; Laurence Arowas; Louise Perrin de Facci; Darragh Duffy; Cliona Ni Cheallaigh; Niall Conlon; Liam Townsend; Heidi Auerswald; Marija Backovic; Bruno Hoen; Arnaud Fontanet; Ivo Mueller; Samira Fafi-Kremer; Timothee Bruel; Michael T White

    doi:10.1101/2021.03.04.21252532 Date: 2021-03-08 Source: medRxiv

    Infection with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. Waning antibody levels lead to reduced sensitivity of serological diagnostic tests over time. This undermines the utility of serological surveillance as the SARS-CoV-2 pandemic progresses into its second year. Here we develop a multiplex serological test for measuring antibodies of three isotypes (IgG, IgM, IgA) to five SARS-CoV-2 antigens (Spike (S), receptor binding domain (RBD), Nucleocapsid (N PROTEIN), Spike subunit 2, Membrane-Envelope fusion) and the Spike proteins PROTEIN of four seasonal coronaviruses. We measure antibody responses in several cohorts of French and Irish hospitalized patients and healthcare workers followed for up to eleven months after symptom onset. The data are analysed with a mathematical model of antibody kinetics to quantify the duration of antibody responses accounting for inter-individual variation. One year after symptoms, we estimate that 36% (95% range: 11%, 94%) of anti-S IgG remains, 31% (9%, 89%) anti-RBD IgG remains, and 7% (1%, 31%) anti-N IgG remains. Antibodies of the IgM isotype waned more rapidly, with 9% (2%, 32%) anti-RBD IgM remaining after one year. Antibodies of the IgA isotype also waned rapidly, with 10% (3%, 38%) anti-RBD IgA remaining after one year. Quantitative measurements of antibody responses were used to train machine learning algorithms for classification of previous infection and estimation of time since infection. The resulting diagnostic test classified previous infections with 99% specificity and 98% (95% confidence interval: 94%, 99%) sensitivity, with no evidence for declining sensitivity over the time scale considered. The diagnostic test also provided accurate classification of time since infection into intervals of 0 - 3 months, 3 - 6 months, and 6 - 12 months. Finally, we present a computational method for serological reconstruction of past SARS-CoV-2 transmission using the data from this test when applied to samples from a single cross-sectional sero-prevalence survey.

    Long-read sequencing of SARS-CoV-2 reveals novel transcripts and a diverse complex transcriptome landscape.

    Authors: Jennifer Li-Pook-Than; Selene Banuelos; Alexander Honkala; Malaya K Sahoo; Benjamin A Pinsky; Michael P Snyder

    doi:10.1101/2021.03.05.434150 Date: 2021-03-06 Source: bioRxiv

    Severe Acute Respiratory Syndrome Coronavirus 2 MESHD, SARS-CoV-2 ( COVID-19 MESHD), is a positive single-stranded RNA virus with a 30 kb genome that is responsible for the current pandemic. To date, the genomes of global COVID-19 MESHD variants have been primarily characterized via short-read sequencing methods. Here, we devised a long-read RNA (IsoSeq) sequencing approach to characterize the COVID-19 MESHD transcript landscape and expression of its [~]27 coding regions. Our analysis identified novel COVID-19 MESHD transcripts including a) a short [~]65-70 nt 5-UTR fused to various downstream ORFs encoding accessory proteins such as the envelope PROTEIN, ORF 8, and ORF 9 HGNC ( nucleocapsid) proteins PROTEIN, that are relatively highly expressed, b) novel SNVs that are differentially expressed, whereby a subset are suggestive of partial RNA editing events, and c) SNVs at functional sites, whereby at least one is associated with a differentially expressed spike protein PROTEIN isoform. These previously uncharacterized COVID-19 MESHD isoforms, expressed genes, and gene variants were corroborated using ddPCR. Understanding this transcriptional complexity may help provide insight into the biology and pathogenicity of SARS-CoV-2 compared to other coronaviruses.

    Inhibition of amyloid formation of the Nucleoprotein PROTEIN of SARS-CoV-2

    Authors: Einav Tayeb-Fligelman; Xinyi Cheng; Christen Tai; Jeannette T. Bowler; Sarah Griner; Michael R. Sawaya; Paul M. Seidler; Yi Xiao Jiang; Jiahui Lu; Gregory M. Rosenberg; Lukasz Salwinski; Romany Abskharon; Chih-Te Zee; Ke Hou; Yan Li; David Boyer; Kevin A. Murray; Genesis Falcon; Daniel H. Anderson; Duilio Cascio; Lorena Saelices; Robert Damoiseaux; Feng Guo; David Eisenberg

    doi:10.1101/2021.03.05.434000 Date: 2021-03-05 Source: bioRxiv

    The SARS-CoV-2 Nucleoprotein PROTEIN (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid-liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid-liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid-liquid phase separation, suggesting a therapeutic route for Covid-19 MESHD.

    The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

    Authors: Darren P Martin; Steven Weaver; Houryiah Tegally; Emmanuel James San; Stephen D Shank; Eduan Wilkinson; Jennifer Giandhari; Sureshnee Naidoo; Yeshnee Pillay; Lavanya Singh; Richard J Lessells; - NGS-SA Consortium; - COVID-19 Genomics UK (COG-UK) Consortium; Ravindra K Gupta; Joel O Wertheim; Anton Nekturenko; Ben Murrell; Gordon W Harkins; Philippe Lemey; Oscar MacLean; David L Robertson; Tulio de Oliveira; Sergei L Kosakovsky Pond

    doi:10.1101/2021.02.23.21252268 Date: 2021-03-05 Source: medRxiv

    The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19 MESHD. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N PROTEIN and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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