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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinE (144)

ProteinS (39)

ProteinN (33)

ComplexRdRp (17)

ProteinM (17)


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SARS-CoV-2 Proteins
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    Altered Sub-Genomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections

    Authors: Matthew D Parker; Benjamin B Lindsey; Dhruv R Shah; Sharon Hsu; Alexander James Keeley; David G Partridge; Shay Leary; Alison Cope; Amy State; Katie Johnson; Nasar Ali; Rasha Raghei; Joe Heffer; Nikki Smith; Peijun Zhang; Marta Gallis; Stavroula F Louka; Max Whiteley; Benjamin H Foulkes; Stella Christou; Paige Wolverson; Manoj Pohare; Sam E Hansford; Luke R Green; Cariad Evans; Mohammad Raza; Dennis Wang; Silvana Gaudieri; Simon Mallal; - The COVID-19 Genomics UK (COG-UK) consortium; Thushan I de Silva

    doi:10.1101/2021.03.02.433156 Date: 2021-03-03 Source: bioRxiv

    SARS-CoV-2 lineage B.1.1.7 viruses are more transmissible, may lead to greater clinical severity, and result in modest reductions in antibody neutralization. subgenomic RNA (sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome and is a crucial step in the SARS-CoV-2 life cycle. Applying our tool (periscope) to ARTIC Network Oxford Nanopore genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA expression profiles are significantly increased in B.1.1.7 infections (n=879). This increase is seen over the previous dominant circulating lineage in the UK, B.1.177 (n=943), which is independent of genomic reads, E gene PROTEIN cycle threshold and day of illness when sampling occurred. A noncanonical subgenomic RNA which could represent ORF9b PROTEIN is significantly enriched in B.1.1.7 SARS-CoV-2 infections MESHD, potentially as a result of a triple nucleotide mutation leading to amino acid substitution D3L in nucleocapsid in this lineage which increases complementarity with the genomic leader sequence. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles in sequence data to evaluate emerging potential variants of concern.

    High-content screening of coronavirus genes for innate immune suppression revealsenhanced potency of SARS-CoV-2 proteins

    Authors: Erika J Olson; David M Brown; Timothy Z Chang; Lin Ding; Tai L Ng; H. Sloane Weiss; Peter Koch; Yukiye Koide; Nathan Rollins; Pia Mach; Tobias Meisinger; Trenton Bricken; Joshus Rollins; Yun Zhang; Colin Molloy; Yun Zhang; Briodget N Queenan; Timothy Mitchison; Debora Marks; Jeffrey C Way; John I Glass; Pamela A Silver

    doi:10.1101/2021.03.02.433434 Date: 2021-03-02 Source: bioRxiv

    Suppression of the host intracellular innate immune system is an essential aspect of viral replication. Here, we developed a suite of medium-throughput high-content cell-based assays to reveal the effect of individual coronavirus proteins on antiviral innate immune pathways. Using these assays, we screened the 196 protein products of seven coronaviruses (SARS-CoV-2,SARS-CoV-1, 229E, NL63, OC43, HKU1 and MERS). This includes a previously unidentified gene in SARS-CoV-2 encoded within the Spike gene. We observe immune-suppressing activity in both known host-suppressing genes (e PROTEIN.g., NSP1, Orf6, NSP3 PROTEIN, and NSP5 PROTEIN) as well as other coronavirus genes, including the newly identified SARS-CoV-2 protein. Moreover, the genes encoded by SARS-CoV-2 are generally more potent immune suppressors than their homologues from the other coronaviruses. This suite of pathway-based and mechanism-agnostic assays could serve as the basis for rapid in vitro prediction of the pathogenicity of novel viruses based on provision of sequence information alone.

    Evaluation of a Sample Pooling Strategy for Sars-cov-2 Using Real Time PCR

    Authors: Annet M Nankya; Luke Nyakarahuka; Stephen Balinandi; John Kayiwa; Julius Lutwama; Andrew Tamale; Joseph M Kungu

    doi:10.21203/rs.3.rs-290291/v1 Date: 2021-03-02 Source: ResearchSquare

    Back ground: Corona Virus Disease MESHD 2019 (COVID 19) in Uganda was first reported in a male traveler from Dubai on 21st March, 2020 shortly after WHO had announced the condition as a global pandemic. Timely laboratory diagnosis of COVID -19 for all samples from both symptomatic and asymptomatic patients was observed as key in containing the pandemic and breaking the chain of transmission. However, there was a challenge of limited resources required for testing SARS-COV-2 in low and middle income countries. To mitigate this, a study was conducted to evaluate a sample pooling strategy for COVI-19 using real time PCR. The cost implication and the turn around time of pooled sample testing versus individual sample testing were also compared.Methods: In this study, 1260 randomly selected samples submitted to Uganda Virus Research Institute for analysis were batched in pools of 5, 10, and 15. The pools were then extracted using a Qiagen kit. Both individual and pooled RNA were screened for the SARS-COV-2 E gene PROTEIN using a Berlin kit. Results: Out of 1260 samples tested, 21 pools were positive in pools of 5 samples, 16 were positive in pools of 10 and 14 were positive in pools of 15 samples. The study also revealed that the pooling strategy helps to save a lot on resources, time and expands diagnostic capabilities without affecting the sensitivity of the test in areas with low SARS-COV-2 prevalence.Conclusion: This study demonstrated that the pooling strategy for COVID-19 MESHD reduced on the turnaround time and there was a substantial increase in the overall testing capacity with limited resources as compared to individual testing.

    Targeted Drug Repurposing Against the SARS-CoV-2 E Channel Identifies Blockers With in vitro Antiviral Activity

    Authors: Prabhat Pratap Singh Tomar; Miriam Krugliak; Isaiah T Arkin

    doi:10.1101/2021.02.24.432490 Date: 2021-02-24 Source: bioRxiv

    It is difficult to overstate the impact that COVID-19 MESHD had on humankind. The pandemic's etiological agent, SARS-CoV-2, is a member of the Coronaviridae, and as such, is an enveloped virus with ion channels in its membrane. Therefore, in an attempt to provide an option to curb the viral spread, we searched for blockers of its E protein PROTEIN viroporin. Using three bacteria-based assays, we identified eight compounds that exhibited activity after screening a library of ca. 3000 approved-for-human-use drugs. Reassuringly, analysis of viral replication in tissue culture indicated that most of the compounds could reduce infectivity to varying extents. In conclusion, targeting a particular channel in the virus for drug repurposing may increase our arsenal of treatment options to combat COVID-19 MESHD virulence.

    Structural Basis for SARS-CoV-2 Envelope Protein PROTEIN in Recognition of Human Cell Junction Protein PALS1

    Authors: Jin Chai; Yuanheng Cai; Changxu Pang; Liguo Wang; Sean McSweeney; John Shanklin; Qun Liu

    doi:10.1101/2021.02.22.432373 Date: 2021-02-23 Source: bioRxiv

    The COVID-19 pandemic MESHD caused by the SARS-CoV-2 virus has created a global health and economic emergency. SARS-CoV-2 viruses hijack human proteins to promote their spread and virulence including the interactions involving the viral envelope (E) protein PROTEIN and human proteins. To understand the structural basis for SARS-CoV-2 viral-host recognition, we used cryo-electron microscopy to determine a structure for the human cell junction protein PALS1 HGNC and SARS-CoV-2 E protein PROTEIN complex. The structure shows that the E protein PROTEIN C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains in PALS1 HGNC. Our structural analysis provides an explanation for the observation that the viral E protein PROTEIN recruits PALS1 HGNC from lung epithelial cell junctions resulting in vascular leakage, lung damage MESHD, viral spread, and virulence. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1 HGNC-E interactions to reduce the E-mediated damage to vascular structures.

    Delivery of recombinant SARS-CoV-2 envelope protein PROTEIN into human cells

    Authors:

    doi:10.1101/2021.02.18.431684 Date: 2021-02-19 Source: bioRxiv

    SARS-CoV-2 envelope protein PROTEIN (S2-E) is a conserved membrane protein that is essential to coronavirus assembly and budding. Here, we describe the recombinant expression and purification of S2-E into amphipol-class amphipathic polymer solutions. The physical properties of amphipols underpin their ability to solubilize and stabilize membrane proteins without disrupting membranes. Amphipol delivery of S2-E to pre-formed planar bilayers results in spontaneous membrane integration and formation of viroporin ion channels. Amphipol delivery of the S2- E protein PROTEIN to human cells results in membrane integration followed by retrograde trafficking to a location adjacent to the endoplasmic reticulum-to-Golgi intermediate compartment (ERGIC) and the Golgi, which are the sites of coronavirus replication. Delivery of S2-E to cells enables both chemical biological approaches for future studies of SARS-CoV-2 pathogenesis MESHD and development of "Trojan Horse" anti-viral therapies. This work also establishes a paradigm for amphipol-mediated delivery of membrane proteins to cells.

    Harnessing recombinase polymerase amplification for rapid detection of SARS-CoV-2 in resource-limited settings

    Authors: Dounia Cherkaoui; Da Huang; Benjamin Miller; Rachel A McKendry

    doi:10.1101/2021.02.17.21251732 Date: 2021-02-19 Source: medRxiv

    The COVID-19 pandemic MESHD has challenged testing capacity worldwide. The mass testing needed to stop the spread of the virus requires new molecular diagnostic tests that are faster and with reduced equipment requirement, but as sensitive as the current gold standard protocols based on polymerase chain reaction. We developed a fast (25-35 minutes) molecular test using reverse transcription recombinase polymerase amplification for simultaneous detection of two conserved regions of the virus, targeting the E and RdRP PROTEIN genes. The diagnostic platform offers two complementary detection methods: real-time fluorescence or visual dipstick. The analytical sensitivity of the test by real-time fluorescence was 9.5 (95% CI: 7.0-18) RNA copies per reaction for the E gene PROTEIN and 17 (95% CI: 11-93) RNA copies per reaction for the RdRP PROTEIN gene. The analytical sensitivity for the dipstick readout was 130 (95% CI: 82-500) RNA copies per reaction. The assay showed high specificity with both detection methods when tested against common seasonal coronaviruses, SARS-CoV and MERS-CoV MESHD model samples. The dipstick readout demonstrated potential for point-of-care testing, with simple or equipment-free incubation methods and a user-friendly prototype smartphone application was proposed with data capture and connectivity. This ultrasensitive molecular test offers valuable advantages with a swift time-to-result and it requires minimal laboratory equipment compared to current gold standard assays. These features render this diagnostic platform more suitable for decentralised molecular testing.

    An alternative approach for bioanalytical assay development for wastewater-based epidemiology of SARS-CoV-2

    Authors: Tim Boogaerts; Lotte Jacobs; Naomi De Roeck; Siel Van den Bogaert; Bert Aertgeerts; Lies Lahousse; Alexander L.N. van Nuijs; Peter Delputte

    doi:10.1101/2021.02.12.21251626 Date: 2021-02-16 Source: medRxiv

    Wastewater-based epidemiology could be applied to track down SARS-CoV-2 outbreaks at high spatio-temporal resolution and could potentially be used as an early-warning for emergence of SARS-CoV-2 circulation in the general population. Epidemiological surveillance of SARS-CoV-2 could play a role in monitoring the spread of the virus in the population and controlling possible outbreaks. However, sensitive sample preparation and detection methods are necessary to detect trace levels of SARS-CoV-2 RNA in influent wastewater (IWW). Unlike predecessors, method development of a SARS-CoV-2 RNA concentration and detection procedure was performed with IWW samples with high viral SARS-CoV-2 loads (in combination with seeding IWW with a surrogate coronavirus). This is of importance since the SARS-CoV-2 genome in IWW might have already been subject to in-sewer degradation into smaller genome fragments or might be present in a different form (e.g. cell debris,...). Centricon Plus-70 (100 kDa) centrifugal filter devices resulted in the lowest and most reproducible Ct-values for SARS-CoV-2 RNA. Lowering pore sizes did not improve our limit of detection and quantification. Real-time polymerase chain reaction (qPCR) was employed for the amplification of the N1, N2, N3 and E_Sarbeco-gene. This is one of the first studies to apply digital polymerase chain reaction (dPCR) for the detection of SARS-CoV-2 RNA in IWW. Interestingly, qPCR results were comparable with dPCR results suggesting that qPCR is a valid method. In this study, dPCR was also used as a proxy to assess the precision of qPCR. In this light, dPCR showed high variability at low concentration levels (100 copies/{micro}L), indicating that variability in bioanalytical assays for SARS-CoV-2 RNA might be substantial. On average, the N2-gene showed high in-sample stability in IWW for 10 days of storage at 4 {degrees}C. Between-sample variability was substantial due to the low native concentrations in IWW. Additionally, the E-gene PROTEIN proved to be less stable compared to the N2-gene and showed higher variability. Freezing the IWW samples resulted in a 10-fold decay of loads of the N2- and E-gene PROTEIN in IWW. Although WBE can already aid in filling some knowledge gaps in the epidemiological surveillance of SARS-CoV-2, future WBE studies should aim to further validate and standardize bioanalytical assays, especially with regards to methodological limitations. HighlightsO_LIDevelopment of an analytical procedure for detection of SARS-CoV-2 RNA in wastewater C_LIO_LIExtraction recovery was evaluated in influent wastewater C_LIO_LIPrecision measured with dPCR used as a proxy for qPCR C_LIO_LIqPCR of the N2 gene fragment showed high in-sample stability of SARS-CoV-2 on average C_LI

    Vaccine Design, Adaptation, and Cloning Design for Multiple Epitope-Based Vaccine Derived From SARS-CoV-2 Surface Glycoprotein (S PROTEIN), Membrane Protein (M PROTEIN) and Envelope Protein (E PROTEIN): In silico approach

    Authors: Peter T. Habib

    doi:10.21203/rs.3.rs-241638/v1 Date: 2021-02-14 Source: ResearchSquare

    The SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global epidemic that has increased the scientific community's concern about developing and finding a counteraction against this lethal virus. So far, hundreds of thousands of people have been infected by the pandemic due to contamination and spread. This research was therefore carried out to develop potential epitope-based vaccines against the SARS-CoV-2 virus using reverse vaccinology and immunoinformatics approaches. Three potential vaccine constructs were designed after intensive computational experimentation, and one vaccine model was chosen as the best vaccine based on a molecular docking analysis that is intended to work efficiently against SARS-CoV-2. In order to verify biological stability and find an appropriate mass production technique for the chosen vaccine, molecular dynamics simulation, and silico codon adaptation studies were subsequently carried out. This study should help to maintain current research efforts to secure a definitive preventive measure against this contagious disease.

    Designing a new multi epitope-based vaccine against COVID-19 MESHD disease: an immunoinformatic study based on reverse vaccinology approach

    Authors: Afshin Samimi Nemati; Majid Tafrihi; Fatemeh Sheikhi; Abolfazl Rostamian Tabari; Amirhossein Haditabar

    doi:10.21203/rs.3.rs-206270/v1 Date: 2021-02-04 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has currently caused a significant pandemic among worldwide populations. The transmission speed and the high rate of mortality caused by the disease necessitate studies for the rapid designing and effective vaccine production. The purpose of this study is to predict and design a novel multi-epitope vaccine against the SARS-CoV-2 virus using bioinformatics approaches. Coronavirus envelope proteins PROTEIN, ORF7b PROTEIN, ORF8 PROTEIN, ORF10 PROTEIN, and NSP9 PROTEIN were selected as targets for epitope mapping using IEDB and BepiPred 2.0 Servers. Also, molecular docking studies were performed to determine the candidate vaccine's affinity to TLR3 HGNC, TLR4 HGNC, MHC I, and MHC II molecules. Thirteen epitopes were selected to construct the multi-epitope vaccine. We found that the constructed peptide has valuable antigenicity, stability, and appropriate half-life. The Ramachandran plot approved the quality of the predicted model after the refinement process. Molecular docking investigations revealed that antibody-mode in the Cluspro 2.0 server showed the lowest binding energy for MHCI, MHCII, TLR3 HGNC, and TLR4 HGNC. This study confirmed that the designed vaccine has a good antigenicity and stability and could be a proper vaccine candidate against the COVID-19 MESHD infectious disease MESHD though, in vitro and in vivo experiments are necessary to complete and confirm our results.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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