Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2

  1. Kui K. Chan
  2. Danielle Dorosky
  3. Preeti Sharma
  4. Shawn A. Abbasi
  5. John M. Dye
  6. David M. Kranz
  7. Andrew S. Herbert
  8. Erik Procko

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Abstract

For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells, the spike protein on the surface of the virus must bind to the host receptor protein, angiotensin-converting enzyme 2 (ACE2). A soluble version of the receptor is being explored as a therapeutic. Chan et al. used deep mutagenesis to identify ACE2 mutants that bind more tightly to the spike protein and combined mutations to further increase binding affinity (see the Perspective by DeKosky). A promising variant was engineered to be a stable dimer that has a binding affinity for the spike protein; it is comparable with neutralizing antibodies and neutralized both SARS-CoV-2 and SARS-CoV-1 in a cell-based assay. In addition, the similarity to the natural receptor may limit the possibility for viral escape.

Science , this issue p. 1261 ; see also p. 1167

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  1. Version published to 10.1126/science.abc0870
  2. ScreenIT

    SciScore for 10.1101/2020.03.16.994236: (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.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cells were washed twice, incubated with secondary antibody (1/100 dilution of chicken anti-HIS-FITC polyclonal from Immunology Consultants Laboratory; or 1/250 anti-human IgG-APC clone HP6017 from BioLegend) for 30 minutes on ice, washed twice again, and fluorescence of the total population after gating by FSC-SSC to exclude debris was measured on a BD Accuri C6.
    anti-HIS-FITC
    suggested: (Miltenyi Biotec Cat# 130-098-808, RRID:AB_2751026)
    anti-human IgG-APC
    suggested: None
    Software and Algorithms
    SentencesResources
    Raw and processed deep sequencing data are deposited in NCBI’s Gene Expression Omnibus (GEO) with series accession no. GSE147194.
    Gene Expression Omnibus
    suggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)

    Results from OddPub: Thank you for sharing your data.

    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

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  3. Version published to 10.1101/2020.03.16.994236v3 on bioRxiv
  4. Version published to 10.1101/2020.03.16.994236v2 on bioRxiv
  5. Version published to 10.1101/2020.03.16.994236v1 on bioRxiv