• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Genome-wide characterization of SARS-CoV-2 cytopathogenic proteins in the search of antiviral targets.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Zhang, Jiantao
    Li, Qi
    Cruz Cosme, Ruth S
    Gerzanich, Vladimir
    Tang, Qiyi
    Simard, J Marc
    Zhao, Richard Y
    Date
    2021-11-24
    Journal
    bioRxiv : the Preprint Server for Biology
    Publisher
    Cold Spring Harbor Laboratory
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1101/2021.11.23.469747
    Abstract
    Therapeutic inhibition of critical viral functions is important for curtailing coronavirus disease-2019 (COVID-19). We sought to identify antiviral targets through genome-wide characterization of SARS-CoV-2 proteins that are crucial for viral pathogenesis and that cause harmful cytopathic effects. All twenty-nine viral proteins were tested in a fission yeast cell-based system using inducible gene expression. Twelve proteins including eight non-structural proteins (NSP1, NSP3, NSP4, NSP5, NSP6, NSP13, NSP14 and NSP15) and four accessory proteins (ORF3a, ORF6, ORF7a and ORF7b) were identified that altered cellular proliferation and integrity, and induced cell death. Cell death correlated with the activation of cellular oxidative stress. Of the twelve proteins, ORF3a was chosen for further study in mammalian cells. In human pulmonary and kidney epithelial cells, ORF3a induced cellular oxidative stress associated with apoptosis and necrosis, and caused activation of pro-inflammatory response with production of the cytokines TNF-α, IL-6, and IFN-β1, possibly through the activation of NF-κB. To further characterize the mechanism, we tested a natural ORF3a Beta variant, Q57H, and a mutant with deletion of the highly conserved residue, ΔG188. Compared to wild type ORF3a, the ΔG188 variant yielded more robust activation of cellular oxidative stress, cell death, and innate immune response. Since cellular oxidative stress and inflammation contribute to cell death and tissue damage linked to the severity of COVID-19, our findings suggest that ORF3a is a promising, novel therapeutic target against COVID-19.
    Keyword
    ORF3a
    SARS-CoV-2
    Schizosaccharomyces pombe
    apoptosis and necrosis
    cellular pro-inflammatory response
    fission yeast
    oxidative stress
    viral therapeutic target
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17569
    ae974a485f413a2113503eed53cd6c53
    10.1101/2021.11.23.469747
    Scopus Count
    Collections
    UMB Coronavirus Publications
    UMB Open Access Articles

    entitlement

    Related articles

    • Genome-Wide Characterization of SARS-CoV-2 Cytopathogenic Proteins in the Search of Antiviral Targets.
    • Authors: Zhang J, Li Q, Cruz Cosme RS, Gerzanich V, Tang Q, Simard JM, Zhao RY
    • Issue date: 2022 Feb 15
    • The role of SARS-CoV-2 accessory proteins in immune evasion.
    • Authors: Zandi M, Shafaati M, Kalantar-Neyestanaki D, Pourghadamyari H, Fani M, Soltani S, Kaleji H, Abbasi S
    • Issue date: 2022 Dec
    • Manipulation of autophagy by SARS-CoV-2 proteins.
    • Authors: Koepke L, Hirschenberger M, Hayn M, Kirchhoff F, Sparrer KM
    • Issue date: 2021 Sep
    • The importance of accessory protein variants in the pathogenicity of SARS-CoV-2.
    • Authors: Hassan SS, Choudhury PP, Dayhoff GW 2nd, Aljabali AAA, Uhal BD, Lundstrom K, Rezaei N, Pizzol D, Adadi P, Lal A, Soares A, Mohamed Abd El-Aziz T, Brufsky AM, Azad GK, Sherchan SP, Baetas-da-Cruz W, Takayama K, Serrano-Aroca Ã, Chauhan G, Palu G, Mishra YK, Barh D, Santana Silva RJ, Andrade BS, Azevedo V, Góes-Neto A, Bazan NG, Redwan EM, Tambuwala M, Uversky VN
    • Issue date: 2022 Mar 15
    • Understanding the Role of SARS-CoV-2 ORF3a in Viral Pathogenesis and COVID-19.
    • Authors: Zhang J, Ejikemeuwa A, Gerzanich V, Nasr M, Tang Q, Simard JM, Zhao RY
    • Issue date: 2022
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.