A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

  1. Yan Wu
  2. Feiran Wang
  3. Chenguang Shen
  4. Weiyu Peng
  5. Delin Li
  6. Cheng Zhao
  7. Zhaohui Li
  8. Shihua Li
  9. Yuhai Bi
  10. Yang Yang
  11. Yuhuan Gong
  12. Haixia Xiao
  13. Zheng Fan
  14. Shuguang Tan
  15. Guizhen Wu
  16. Wenjie Tan
  17. Xuancheng Lu
  18. Changfa Fan
  19. Qihui Wang
  20. Yingxia Liu
  21. Chen Zhang
  22. Jianxun Qi
  23. George Fu Gao
  24. Feng Gao
  25. Lei Liu

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Abstract

One of the responses of the immune system to invading viruses is the production of antibodies. Some of these are neutralizing, meaning that they prevent the virus from being infectious, and can thus be used to treat viral diseases. Wu et al. isolated four neutralizing antibodies from a convalescent coronavirus disease 2019 (COVID-19) patient. Two of the antibodies, B38 and H4, blocked the receptor binding domain (RBD) of the viral spike protein from binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). The structure of the RBD bound to B38 shows that the B38-binding site overlaps with the binding site for ACE2. Although H4 also blocks RBD binding to ACE2, it binds at a different site, and thus the two antibodies can bind simultaneously. This pair of antibodies could potentially be used together in clinical applications.

Science , this issue p. 1274

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  1. Version published to 10.1126/science.abc2241
  2. ScreenIT

    SciScore for 10.1101/2020.05.01.20077743: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All the procedures in the murine study were reviewed and approved by the Laboratory Animal Welfare and Ethics Committee in Chinese Academy of Sciences.
    Consent: The donor provided written informed consent for the use of blood and blood components followed the approval from the Research Ethics Committee of ShenZhen Third People’s Hospital,
    IRB: The donor provided written informed consent for the use of blood and blood components followed the approval from the Research Ethics Committee of ShenZhen Third People’s Hospital,
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAnimal experiments: Twelve female hACE2 transgenic mice (5-6 weeks old) were divided into three groups with four mice in each group.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Bio-Layer Interferometry (BLI): The antibody binding screening and the competitive binding of mAbs and hACE2 (or between two antibodies) were measured by BLI using the Octet RED96 system (FortéBio).
    hACE2
    suggested: None
    A CM5 chip (GE Healthcare) was coupled with anti-human Fc antibody to capture the antibodies at 8000 response units.
    anti-human Fc
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cells and Viruses: HEK293T (ATCC CRL-3216) cells and Vero (ATCC CCL-81TM) cells were cultured at 37 °C with 5% CO2 in Dulbecco’s Modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS).
    Vero
    suggested: None
    Vero E6 cells were applied to the amplification and titer titration of the virus stocks.
    Vero E6
    suggested: RRID:CVCL_XD71)
    The plasmids of B38 heavy chain and light chain were co-transfected into HEK293T cells to produce B38 IgG.
    HEK293T
    suggested: None
    For the antibody binding screening assay, 293T cell derived antibodies supernatants were loaded onto AHC biosensors for 120 s and flowed with 500 nM COVID-19 virus RBD or 1µM SARS-CoV RBD.
    293T
    suggested: None
    Software and Algorithms
    SentencesResources
    The dataset was processed with HKL2000 software(21).
    HKL2000
    suggested: None
    The complex structure was determined by the molecular replacement method using Phaser with our previously reported hCoV-2 RBD structure (PDB code, 6LZG) and Fab structure (PDB code, 4TSA).
    Phaser
    suggested: (Phaser, RRID:SCR_014219)
    All the figures were prepared with Pymol software (http://www.pymol.org).
    Pymol
    suggested: (PyMOL, RRID:SCR_000305)
    The values of IC50 were calculated using prism software (GraphPad).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 25. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  3. Version published to 10.1101/2020.05.01.20077743v2 on medRxiv
  4. Version published to 10.1101/2020.05.01.20077743v1 on medRxiv