• SARS-CoV-2 spike protein more stable, sl

    From ScienceDaily@1:317/3 to All on Wednesday, March 30, 2022 22:30:46
    SARS-CoV-2 spike protein more stable, slower changing than earlier
    version

    Date:
    March 30, 2022
    Source:
    University of Arkansas
    Summary:
    New computational simulations of the behavior of SARS-CoV-1
    and SARS-CoV- 2 spike proteins prior to fusion with human cell
    receptors show that SARS-CoV-2, the virus that causes COVID-19,
    is more stable and slower changing than the earlier version that
    caused the SARS epidemic in 2003.



    FULL STORY ==========================================================================
    New computational simulations of the behavior of SARS-CoV-1 and SARS-CoV-
    2 spike proteins prior to fusion with human cell receptors show that
    SARS-CoV- 2, the virus that causes COVID-19, is more stable and slower
    changing than the earlier version that caused the SARS epidemic in 2003.


    ========================================================================== Severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and
    SARS- CoV-2) have striking similarities, and researchers do not fully understand why the latter has been more infectious.

    The spike proteins of each, which bind to host cell angiotensin converting enzyme 2, otherwise known as the human cell receptor, have been targeted
    as the potential source of the different transmissibility. Understanding
    the mechanistic details of the spike proteins prior to binding could
    lead to the development of better vaccines and medications.

    The new finding does not necessarily mean that SARS-CoV-2 is more likely
    to bind to cell receptors, but it does mean that its spike protein has
    a better chance of effective binding.

    "Once it finds the cell receptor and binds to it, the SARS-CoV-2 spike
    is more likely to stay bound until the rest of the necessary steps are completed for full attachment to the cell and initiation of cell entry,"
    said Mahmoud Moradi, associate professor of chemistry and biochemistry
    in the Fulbright College of Arts and Sciences.

    To determine differences in conformational behavior between the two
    versions of the virus, Moradi's research team performed an extensive set
    of equilibrium and nonequilibrium simulations of the molecular dynamics
    of SARS-CoV-1 and SARS- CoV-2 spike proteins, leading up to binding with
    cell angiotensin converting enzyme 2. The 3D simulations were done on a microsecond-level, using computational resources provided by the COVID-19
    High Performance Computing Consortium.

    Equilibrium simulations allow the models to evolve spontaneously on their
    own time, while nonequilibrium simulations use external manipulation to
    induce the desired changes in a system. The former is less biased, but
    the latter is faster and allows for many more simulations to run. Both methodological approaches provided a consistent picture, independently demonstrating the same conclusion that the SARS-CoV-2 spike proteins
    were more stable.

    The models revealed other important findings, namely that the energy
    barrier associated with activation of SARS-CoV-2 was higher, meaning the binding process happened slowly. Slow activation allows the spike protein
    to evade human immune response more efficiently, because remaining in an inactive state longer means the virus cannot be attacked by antibodies
    that target the receptor binding domain.

    Researchers understand the importance of the so-called receptor-binding
    domain, or RBD, which is the critical part of a virus that allows it to
    dock to human cell receptors and thus gain entry into cells and cause infection. Models produced by Moradi's team confirm the importance of
    the receptor-binding domain but also suggest that other domains, such
    as the N-terminal domain, could play a crucial role in the different
    binding behavior of SARS-CoV-1 and -2 spike proteins.

    N-terminal domain of a protein is a domain located at the N-terminus or
    simply the start of the polypeptide chain, as opposed to the C-terminus,
    which is the end of the chain. Though it is near the receptor-binding
    domain and is known to be targeted by some antibodies, function of the N-terminal domain in SARS-CoV- 1 and -2 spike proteins is not completely understood. Moradi's team is the first to find evidence for potential interaction of the N-terminal domain and the receptor binding domain.

    "Our study sheds light on the conformational dynamics of the SARS-CoV-1
    and SARS-CoV-2 spike proteins," Moradi said. "Differences in the
    dynamic behavior of these spike proteins almost certainly contribute to differences in transmissibility and infectivity." The researchers' study, "Prefusion Spike Protein Conformational Changes Are Slower in SARS-CoV-2
    than SARS-Cov-1," was published inJournal of Biological Chemistry.


    ========================================================================== Story Source: Materials provided by University_of_Arkansas. Original
    written by Matt McGowan.

    Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Vivek Govind Kumar, Dylan S. Ogden, Ugochi H. Isu, Adithya Polasa,
    James
    Losey, Mahmoud Moradi. Prefusion Spike Protein Conformational
    Changes Are Slower in SARS-CoV-2 than in SARS-CoV-1. Journal of
    Biological Chemistry, 2022; 101814 DOI: 10.1016/j.jbc.2022.101814 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220330141318.htm

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