A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells

  1. Zhaoqian Su
  2. Yinghao Wu

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Abstract

The respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than one million death globally since December 2019. This new virus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the same receptor called Angiotensin-converting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than SARS-CoV-2. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from SARS-CoV-2, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that this new pandemic by far spread much faster than SARS.

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  1. Version published to 10.1101/2020.02.20.958272v2 on bioRxiv
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    SciScore for 10.1101/2020.02.20.958272: (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
    In detail, the atomic structure of SARS-CoV-2 S-protein RBD domain was first predicted by I-TASSER [38] based on the newly released sequence of SARS-CoV-2 [39].
    I-TASSER
    suggested: (I-TASSER, RRID:SCR_014627)

    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.

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  3. Version published to 10.1101/2020.02.20.958272v1 on bioRxiv