Protein Scaffold‐Based Multimerization of Soluble ACE2 Efficiently Blocks SARS‐CoV‐2 Infection In Vitro and In Vivo

  1. Alisan Kayabolen
  2. Ugur Akcan
  3. Doğancan Özturan
  4. Hivda Ulbegi‐Polat
  5. Gizem Nur Sahin
  6. Nareg Pinarbasi‐Degirmenci
  7. Canan Bayraktar
  8. Gizem Soyler
  9. Ehsan Sarayloo
  10. Elif Nurtop
  11. Berna Ozer
  12. Gulen Guney‐Esken
  13. Tayfun Barlas
  14. Ismail Selim Yildirim
  15. Ozlem Dogan
  16. Sercin Karahuseyinoglu
  17. Nathan A. Lack
  18. Mehmet Kaya
  19. Cem Albayrak
  20. Fusun Can
  21. Ihsan Solaroglu
  22. Tugba Bagci‐Onder

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Abstract

Soluble ACE2 (sACE2) decoys are promising agents to inhibit SARS‐CoV‐2, as their efficiency is unlikely to be affected by escape mutations. However, their success is limited by their relatively poor potency. To address this challenge, multimeric sACE2 consisting of SunTag or MoonTag systems is developed. These systems are extremely effective in neutralizing SARS‐CoV‐2 in pseudoviral systems and in clinical isolates, perform better than the dimeric or trimeric sACE2, and exhibit greater than 100‐fold neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag fused to a more potent sACE2 (v1) achieves a sub‐nanomolar IC 50 , comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutations for variants of concern, including delta and omicron, are also neutralized efficiently with multimeric sACE2. Finally, therapeutic treatment of sACE2(v1)‐MoonTag provides protection against SARS‐CoV‐2 infection in an in vivo mouse model. Therefore, highly potent multimeric sACE2 may offer a promising treatment approach against SARS‐CoV‐2 infections.

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  1. Version published to 10.1002/advs.202201294
  2. Version published to 10.1101/2021.01.04.425128v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.01.04.425128: (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: 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

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  4. Version published to 10.1101/2021.01.04.425128v1 on bioRxiv