Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2

  1. Cheng Wang
  2. Shaobo Wang
  3. Daixi Li
  4. Xia Zhao
  5. Songling Han
  6. Tao Wang
  7. Gaomei Zhao
  8. Yin Chen
  9. Fang Chen
  10. Jianqi Zhao
  11. Liting Wang
  12. Wei Sun
  13. Yi Huang
  14. Yongping Su
  15. Dongqing Wei
  16. Jinghong Zhao
  17. Junping Wang

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Abstract

The burgeoning epidemic caused by novel coronavirus 2019 (2019-nCoV) is currently a global concern. Angiotensin-converting enzyme-2 (ACE2) is a receptor of 2019-nCoV spike 1 protein (S1) and mediates viral entry into host cells. Despite the abundance of ACE2 in small intestine, few digestive symptoms are observed in patients infected by 2019-nCoV. Herein, we investigated the interactions between ACE2 and human defensins (HDs) specifically secreted by intestinal Paneth cells. The lectin-like HD5, rather than HD6, bound ACE2 with a high affinity of 39.3 nM and weakened the subsequent recruitment of 2019-nCoV S1. The cloak of HD5 on the ligand-binding domain of ACE2 was confirmed by molecular dynamic simulation. A remarkable dose-dependent preventive effect of HD5 on 2019-nCoV S1 binding to intestinal epithelial cells was further evidenced by in vitro experiments. Our findings unmasked the innate defense function of lectin-like intestinal defensin against 2019-nCoV, which may provide new insights into the prevention and treatment of 2019-nCoV infection.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.29.013490: (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
    A primary anti-spike rabbit monoclonal antibody (40150-R007, Sino Biological, 1:100) and a goat anti-rabbit secondary antibody (Alexa Fluor 488, Invitrogen, Thermo Fisher Scientific) were employed to stain 2019-nCoV S1.
    anti-spike
    suggested: (Sino Biological Cat# 40150-R007, RRID:AB_2827979)
    anti-rabbit
    suggested: None
    S1
    suggested: None
    A primary anti-His-tag mouse monoclonal antibody (AF5060, Beyotime, 1:1000) and a goat anti-mouse secondary antibody (A0216, Beyotime, 1:2000) were employed to detect S1.
    anti-His-tag
    suggested: (AnaSpec; EGT Group Cat# 29673-1000, RRID:AB_11232932)
    anti-mouse
    suggested: (Beyotime Cat# A0216, RRID:AB_2860575)
    β-actin determined by a mouse monoclonal antibody (AA128, Beyotime, 1:1000) was used as a reference.
    AA128
    suggested: (Beyotime Cat# AA128, RRID:AB_2861213)
    Experimental Models: Cell Lines
    SentencesResources
    Immunofluorescence microscopy: Caco-2 and HK-2 obtained from the cell bank of Chinese Academy of Sciences (CAS, Shanghai) and cultured in Dulbecco’s modified Eagle medium (DMEM, Gibco, Thermo Fisher Scientific, Shanghai
    Caco-2
    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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 10.1101/2020.03.29.013490v1 on bioRxiv