The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor

  1. Esther S. Brielle
  2. Dina Schneidman-Duhovny
  3. Michal Linial

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Abstract

The COVID-19 disease has plagued over 110 countries and has resulted in over 4,000 deaths within 10 weeks. We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2–ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to SARS-CoV. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications on therapeutic strategies.

One Sentence Summary

Molecular dynamics simulations reveal a temporal dimension of coronaviruses interactions with the host receptor.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.10.986398: (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
    Missing residues were added in MODELLER.
    MODELLER
    suggested: (MODELLER, RRID:SCR_008395)
    Interaction scores between the virus spike RBD and ACE2 were calculated for each frame of the trajectory using the SOAP statistical potential (16).
    SOAP
    suggested: (SOAP, RRID:SCR_000689)

    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 10.1101/2020.03.10.986398v1 on bioRxiv