High-Potency Polypeptide-based Inhibition of Enveloped-virus Glycoproteins

  1. Jianpeng Ma
  2. Adam Campos Acevedo
  3. Qinghua Wang

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Abstract

Specific manipulation of proteins post-translationally remains difficult. Here we report results of a general approach that uses a partial sequence of a protein to efficiently modulate the expression level of the native protein. When applied to coronavirus, human immunodeficiency virus, Ebolavirus, respiratory syncytial virus and influenza virus, polypeptides containing highly conserved regions of the viral glycoproteins potently diminished expression of the respective native proteins. In the cases of coronavirus and influenza virus where multiple strains were tested, the polypeptides were equally effective against glycoproteins of other coronavirus and influenza strains with sequence identity as low as 27%, underscoring their high insensitivity to mutations. Thus, this method provides a platform for developing high-efficacy broad-spectrum anti-viral inhibitors, as well as a new way to alter expression of essentially any systems post-translationally.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.05.438537: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    C9-rhodopsin antibody 1D4 HRP (Cat. No. sc57432 HRP) and 2’,3’-cyclinc nucleotide 3’-phosphodiesterase (CNPase) antibody (Cat. No. A01308) were purchased from Santa Cruz Biotechnology, Inc. (Dallas, TX, USA) and Genscript Biotech (Piscataway, NJ, USA), respectively.
    2’,3’-cyclinc nucleotide 3’-phosphodiesterase (CNPase) antibody
    suggested: None
    2’,3’-cyclinc nucleotide 3’-phosphodiesterase (CNPase)
    suggested: None
    The cleared lysate (“Whole cell” fraction) and eluted proteins (“Cell surface” fraction) were run on 10% SDS-PAGE and the spike proteins were detected by C9-rhodopsin antibody 1D4 HRP.
    C9-rhodopsin
    suggested: None
    Endogenous membrane-anchored protein CNPase was detected by anti-CNPase antibody and served as an internal control.
    anti-CNPase
    suggested: None
    The virus lysate was analyzed by western blot using rhodopsin antibody 1D4 HRP for spike proteins, and FITC-conjugated anti-p24 mAb and HRP-conjugated anti-FITC mAb for p24, which served as an internal control.
    anti-p24
    suggested: None
    anti-FITC
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Luciferase assay of cell entry by pseudoviruses: HEK293T cells were seeded on 100 mm dishes the night before.
    HEK293T
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.04.05.438537 on bioRxiv