Spike Protein Targeting “Nano-Glue” that Captures and Promotes SARS-CoV-2 Elimination

  1. Guofang Zhang
  2. Yalin Cong
  3. Guoli Cao
  4. Liang Li
  5. Peng Yu
  6. Qingle Song
  7. Ke Liu
  8. Jing Qu
  9. Jing Wang
  10. Wei Xu
  11. Shumin Liao
  12. Yunping Fan
  13. Yufeng Li
  14. Guocheng Wang
  15. Lijing Fang
  16. Yanzhong Chang
  17. Yuliang Zhao
  18. Diana Boraschi
  19. Hongchang Li
  20. Chunying Chen
  21. Liming Wang
  22. Yang Li

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Abstract

The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein with abundant β-sheet structure serves as target for COVID-19 therapeutic drug design. Here, we discovered that ultrathin 2D CuInP 2 S 6 (CIPS) nanosheets as a new agent against SARS-CoV-2 infection, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike protein, with consequent inhibition of virus entry and infection in ACE2-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein ( K D < 1 pM) with negligible toxicity in vitro and in vivo . Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.13.439641: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: All the human tissue-related work was approved by the ethics committee of the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen (No. 0720) and the ethics committee of Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (SIAT-IRB-200215-H0415).
    Consent: Written informed consents were obtained from all participating patients.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Antiviral effect of CIPS on Vero-E6 cells with SARS-CoV-2 post-infection: Vero-E6 cells were seeded in 24-well plate overnight with a density of 5×104 cells/well.
    Vero-E6
    suggested: None
    CIPS effects on SC2-P elimisnation and infection of THP-1 differentiated macrophages: The THP-1 cells were seeded in a 24-well plate with cover slide at a density of 5×104 cell/well (for elimination), or in a 96-well plate at a density of 1×104 cell/well (for infection), and treated with 100 ng/ml PMA 24 h for macrophage differentiation.
    THP-1
    suggested: None
    Software and Algorithms
    SentencesResources
    The occupied space of the cells was analyzed by ImageJ and shown as percentage of the area fraction covered by cells, as an estimate of intact healthy cells in the image.
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)

    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 10.1101/2021.04.13.439641 on bioRxiv