Comparison of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Binding to ACE2 Receptors from Human, Pets, Farm Animals, and Putative Intermediate Hosts

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Abstract

SARS-CoV-2 is threatening people worldwide, and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear, and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes, indicating that the species barrier might be low. Exceptions are dogs and especially pigs, which revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.

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  1. SciScore for 10.1101/2020.05.08.084061: (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

    Software and Algorithms
    SentencesResources
    All the sequences were aligned using MEGA7.0.
    MEGA7.0
    suggested: None
    Structural analysis: The software PyMol was used to create the figures of the Cryo-EM structure of S from SARS-CoV-2 (pdb file 6VSB) and from the crystal structure of its receptor-binding domain bound to human ACE2 (pdb file 6M0J).
    PyMol
    suggested: (PyMOL, RRID:SCR_000305)
    Statistical analyses were performed using Student’s t-test using GraphPad Prism 5 software.
    GraphPad Prism
    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: 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

    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.

  2. SciScore for 10.1101/2020.05.08.084061: (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.Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Comparison of the interacting surface of ACE2 proteins that serve and not serve as SARS-CoV-2 receptor It has been shown that transfection of HeLa cells with genes encoding the human, pig, civet, and bat ACE2 receptor makes them susceptible to infection with SARS-CoV-2, but not with ACE2 from mice (12).
    HeLa
    suggested: CLS Cat# 300194/p772_HeLa, CVCL_0030
    Software and Algorithms
    SentencesResources
    Here, we used recently released X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2.
    SARS-CoV-2
    suggested: (Sino Biological Cat# 40143-R019, AB_2827973)
    Sequences were aligned using MEGA7.0.
    MEGA7.0
    suggested: None
    Structural analysis The software PyMol was used to create the figures of the Cryo-EM structure of S from SARS-CoV-2 (pdb file 6VSB) and from the crystal structure of its receptor-binding domain bound to human ACE2 (pdb file 6M0J).
    PyMol
    suggested: (PyMOL, SCR_000305)
    Statistical analyses were performed using Student’s t-test using GraphPad Prism 5 software.
    GraphPad Prism
    suggested: (GraphPad Prism, SCR_002798)
    ACKNOWLEDGMENTS This work was financially supported by the National Key Research and Development Program of China (2017YFD0500101), the Fundamental Research Funds for the Central Universities Y0201900459, the Young Top-Notch Talents of National Ten-Thousand Talents Program, Sino German cooperation and exchange project in international cooperation and Cultivation Project in 2019.
    National Ten-Thousand Talents Program
    suggested: None

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.