De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2

  1. Thomas W. Linsky
  2. Renan Vergara
  3. Nuria Codina
  4. Jorgen W. Nelson
  5. Matthew J. Walker
  6. Wen Su
  7. Christopher O. Barnes
  8. Tien-Ying Hsiang
  9. Katharina Esser-Nobis
  10. Kevin Yu
  11. Z. Beau Reneer
  12. Yixuan J. Hou
  13. Tanu Priya
  14. Masaya Mitsumoto
  15. Avery Pong
  16. Uland Y. Lau
  17. Marsha L. Mason
  18. Jerry Chen
  19. Alex Chen
  20. Tania Berrocal
  21. Hong Peng
  22. Nicole S. Clairmont
  23. Javier Castellanos
  24. Yu-Ru Lin
  25. Anna Josephson-Day
  26. Ralph S. Baric
  27. Deborah H. Fuller
  28. Carl D. Walkey
  29. Ted M. Ross
  30. Ryan Swanson
  31. Pamela J. Bjorkman
  32. Michael Gale
  33. Luis M. Blancas-Mejia
  34. Hui-Ling Yen
  35. Daniel-Adriano Silva

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Abstract

Many efforts to develop therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are focused on the interaction between the spike protein, which decorates the surface of the virus, and its host receptor, human angiotensin-converting enzyme 2 (hACE2). Linsky et al. describe a de novo design strategy that allowed them to engineer decoy proteins that bind to the spike protein by replicating the hACE2 interface. The best decoy, CTC-445, bound with low nanomolar affinity, and selection of viral mutants that decrease binding is unlikely because this would also affect binding to hACE2. A bivalent version of CTC-445 bound even more tightly, neutralized SARS-CoV-2 infection of cells, and protected hamsters from a SARS-CoV-2 challenge. The stable decoy has the potential for respiratory therapeutic delivery.

Science , this issue p. 1208

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    SciScore for 10.1101/2020.08.03.231340: (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

    No key resources detected.

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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  2. Version published to 10.1126/science.abe0075
  3. Version published to 10.1101/2020.08.03.231340v1 on bioRxiv