Evolutionary differences in the ACE2 reveals the molecular origins of COVID-19 susceptibility

  1. Ryan R. Cheng
  2. Esteban Dodero-Rojas
  3. Michele Di Pierro
  4. José N. Onuchic

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Abstract

We explore the energetic frustration patterns associated with the binding between the SARS-CoV-2 spike protein and the ACE2 receptor protein in a broad selection of animals. Using energy landscape theory and the concept of energy frustration—theoretical tools originally developed to study protein folding—we are able to identify interactions among residues of the spike protein and ACE2 that result in COVID-19 resistance. This allows us to identify whether or not a particular animal is susceptible to COVID-19 from the protein sequence of ACE2 alone. Our analysis predicts a number of experimental observations regarding COVID-19 susceptibility, demonstrating that this feature can be explained, at least partially, on the basis of theoretical means.

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  1. Version published to 10.1101/2021.03.25.437113v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.03.25.437113: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The full length protein sequences of the ACE2 proteins for mouse (Mus musculus), ferret (Mustela putorius furo), chicken (Gallus gallus domesticus), pig (Sus), duck (Anas platyrhynchos), Syrian golden hamster (Mesocricetus auratus), and mink (Neovison vison) were obtained from the Uniprot database[29] to supplement the sequences derived from the DNA Zoo.
    Uniprot
    suggested: (UniProtKB, RRID:SCR_004426)
    For comparative analysis, a multiple sequence alignment was generated for the ACE2 sequences using Clustal Omega[30].
    Clustal Omega[30
    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 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 10.1101/2021.03.25.437113v1 on bioRxiv