Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins

  1. Sai Anand
  2. Yaozong Chen
  3. Jérémie Prévost
  4. Romain Gasser
  5. Guillaume Beaudoin-Bussières
  6. Cameron Abrams
  7. Marzena Pazgier
  8. Andrés Finzi

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Abstract

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is responsible for the current global coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. A better understanding of the spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. We show that there exist differential inter-protomer conformational transitions between both spike trimers. Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restraints. Our findings can be of importance in the development of therapeutics that block the spike/ACE2 interaction.

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  1. Version published to 10.3390/v12101104
  2. ScreenIT

    SciScore for 10.1101/2020.09.07.286567: (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 AuthenticationAuthentication: The presence of the desired mutations was determined by automated DNA sequencing.

    Table 2: Resources

    Antibodies
    SentencesResources
    goat anti-human IgG (H+L) Ab (Invitrogen) and AlexaFluor-647-conjugated donkey anti-goat IgG (H+L) Ab (Invitrogen) were used as secondary antibodies.
    anti-human IgG
    suggested: None
    AlexaFluor-647-conjugated donkey anti-goat IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The generation and maintenance of 293T-ACE2 cell line was previously reported [22].
    293T-ACE2
    suggested: RRID:CVCL_YZ65)
    Briefly, 293T cells were transfected by the calcium phosphate method with the lentiviral vector pNL4.3 R-E-Luc (NIH AIDS Reagent Program) and a plasmid encoding for SARS-CoV-2 Spike (WT or D614G), SARS-CoV-1 Spike or VSV-G at a ratio of 5:4.
    293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Samples were acquired on a LSRII cytometer (BD Biosciences, Mississauga, ON, Canada) and data analysis was performed using FlowJo vX.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Hill coefficient analyses were done with using GraphPad Prism version 8.0.1 (GraphPad, San Diego, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04335136CompletedRecombinant Human Angiotensin-converting Enzyme 2 (rhACE2) a…

    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.

  3. Version published to 10.1101/2020.09.07.286567v1 on bioRxiv