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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinE (43)

ProteinS (15)

ProteinN (9)

ProteinM (8)

ORF1ab (3)


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SARS-CoV-2 Proteins
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    Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry MESHD

    Authors: Shiyou Zhu; Ying Liu; Zhuo Zhou; Zhiying Zhang; Xia Xiao; Zhiheng Liu; Ang Chen; Xiaojing Dong; Feng Tian; Shihua Chen; Yiyuan Xu; Chunhui Wang; Qiheng Li; Xuran Niu; Qian Pan; Shuo Du; Junyu Xiao; Jianwei Wang; Wensheng Wei

    doi:10.1101/2021.04.08.438924 Date: 2021-04-09 Source: bioRxiv

    The ongoing pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects MESHD a variety of tissues where the known receptor ACE2 HGNC is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection MESHD. In addition to known host proteins, i.e PROTEIN. ACE2 HGNC, TMPRSS2 HGNC, and NRP1 HGNC, we identified multiple host components, among which LDLRAD3 HGNC, TMEM30A HGNC, and CLEC4G HGNC were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain ( NTD HGNC). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 HGNC and CLEC4G HGNC mediate SARS-CoV-2 entry MESHD and infection in a fashion independent of ACE2 HGNC. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19 MESHD.

    Altered O-glycosylation Level of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN Protein by Host O-glycosyltransferase Strengthens Its Trimeric Structure

    Authors: Zhijue Xu; Xin Ku; Jiaqi Tian; Han Zhang; Jingli Hou; Can Zhang; Jingjing Shi; Yang Li; Hiroyuki Kaji; Sheng-ce Tao; Atsushi Kuno; Wei Yan; Lin-Tai Da; Yan Zhang

    doi:10.1101/2021.04.06.438614 Date: 2021-04-06 Source: bioRxiv

    The trimeric spike protein (S PROTEIN) mediates host-cell entry and membrane fusion of SARS-CoV-2. S protein PROTEIN is highly glycosylated, whereas its O-glycosylation is still poorly understood. Herein, we site-specifically examine the O-glycosylation of S protein PROTEIN through a mass spectrometric approach with HCD MESHD-triggered-ETD model. We identify 15 high-confidence O-glycosites and at least 10 distinct O-glycan structures on S protein PROTEIN. Peptide microarray assays prove that human ppGalNAc-T6 actively participates in O-glycosylation of S protein PROTEIN. Importantly, the upregulation of ppGalNAc-T6 expression can profoundly enhance the O-glycosylation level by generating new O-glycosites and increasing both O-glycan heterogeneity and intensities. Further molecular dynamics simulations reveal that the O-glycosylation on the protomer-interface regions, which are mainly modified by ppGalNAc-T6, can potentially stabilize the trimeric S protein PROTEIN structure. Our work provides deep molecular insights of how viral infection harnesses the host O-glycosyltransferases MESHD to dynamically regulate the O-glycosylation level of the viral envelope protein PROTEIN responsible for membrane fusion.

    S-acylation controls SARS-Cov-2 membrane lipid organization and enhances infectivity MESHD

    Authors: Francisco Sarmento Mesquita; Laurence Abrami; Oksana Sergeeva; Priscilla Turelli; Beatrice Kunz; Charlene Raclot; Jonathan Paz Montoya; Luciano Abriata; Matteo Dal Peraro; Didier Trono; F. Gisou van der Goot

    doi:10.1101/2021.03.14.435299 Date: 2021-03-15 Source: bioRxiv

    SARS-CoV-2 virions are surrounded by a lipid bilayer which contains membrane proteins such as Spike PROTEIN, responsible for target-cell binding and virus fusion, the envelope protein E PROTEIN and the accessory protein Orf3a PROTEIN. Here, we show that during SARS-CoV-2 infection MESHD, all three proteins become lipid modified, through action of the S- acyltransferase ZDHHC20 HGNC. Particularly striking is the rapid acylation of Spike on 10 cytosolic cysteines within the ER and Golgi. Using a combination of computational, lipidomics and biochemical approaches, we show that this massive lipidation controls Spike biogenesis and degradation, and drives the formation of localized ordered cholesterol and sphingolipid rich lipid nanodomains, in the early Golgi where viral budding occurs. ZDHHC20 HGNC-mediated acylation allows the formation of viruses with enhanced fusion capacity and overall infectivity. Our study points towards S-acylating enzymes and lipid biosynthesis enzymes as novel therapeutic anti-viral targets.

    Comparative studies of the seven human coronavirus envelope proteins PROTEIN using topology prediction and molecular modelling to understand their pathogenicity

    Authors: Dewald Schoeman; Ruben Cloete; Burtram Fielding

    doi:10.1101/2021.03.08.434384 Date: 2021-03-08 Source: bioRxiv

    Human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 are less virulent and cause mild, self-limiting respiratory tract infections, while SARS-CoV MESHD, MERS-CoV, and SARS-CoV-2, are more virulent and have caused severe outbreaks. The CoV envelope (E) protein PROTEIN, an important contributor to the pathogenesis of severe hCoVs infections MESHD, may provide insight into this disparate severity of the disease. Topology prediction programs and 3D modelling software was used to predict and visualize structural aspects of the hCoV E protein PROTEIN related to its functions. All seven hCoV E proteins PROTEIN largely adopted different topologies, with some distinction between the more virulent and less virulent ones. The 3D models refined this distinction, showing the PDZ-binding motif (PBM) of SARS-CoV MESHD, MERS-CoV, and SARS-CoV-2 to be more flexible than the PBM of hCoVs 229E, NL63, OC43, and HKU1. We speculate that the increased flexibility of the PBM may provide the more virulent hCoVs with a greater degree of freedom, which can allow them to bind to different host proteins and can contribute to a more severe form of the disease. This is the first paper to predict the topologies and model 3D structures of all seven hCoVs E proteins PROTEIN, providing novel insights for possible drug and/or vaccine development.

    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.

    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.

    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.

    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.

    Expression of human ACE2 HGNC N-terminal domain, part of the receptor for SARS-CoV-2, in fusion with maltose binding protein, E PROTEIN. coli ribonuclease I and human RNase A

    Authors: Shuang-yong Xu; Alexey Fomenkov; Tien-Hao Chen; Erbay Yigit; Yinhui Lu; Karl E Kadler

    doi:10.1101/2021.01.31.429007 Date: 2021-02-01 Source: bioRxiv

    The SARS-CoV-2 viral genome contains a positive-strand single-stranded RNA of ~30 kb. Human ACE2 HGNC protein is the receptor for SARS-CoV-2 virus attachment MESHD and initiation of infection MESHD. We propose to use ribonucleases (RNases) as antiviral agents to destroy the viral genome in vitro. In the virions the RNA is protected by viral capsid proteins, membrane proteins and nucleocapsid PROTEIN proteins. To overcome this protection we set out to construct RNase fusion with human ACE2 HGNC receptor N-terminal domain (ACE2NTD). We constructed six proteins expressed in E. coli cells: 1) MBP-ACE2NTD, 2) ACE2NTD-GFP, 3) RNase I (6xHis), 4) RNase III (6xHis), 5) RNase I-ACE2NTD (6xHis), and 6) human RNase A HGNC-ACE2NTD150 (6xHis). We evaluated fusion expression in different E. coli strains, partially purified MBP-ACE2NTD protein from the soluble fraction of bacterial cell lysate, and refolded MBP-ACE2NTD protein from inclusion body. The engineered RNase I-ACE2NTD (6xHis) and hRNase A-ACE2NTD (6xHis) fusions are active in cleaving COVID-19 MESHD RNA in vitro. The recombinant RNase I (6xHis) and RNase III (6xHis) are active in cleaving RNA and dsRNA in test tube. This study provides a proof-of-concept for construction of fusion protein between human cell receptor and nuclease that may be used to degrade viral nucleic acids in our environment.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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