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    Home > Active Ingredient News > Infection > Science first released the molecular level analysis of the Omicron spike protein, revealing the two major reasons for increased infectivity, The Lancet: The global pandemic is expected to end in March

    Science first released the molecular level analysis of the Omicron spike protein, revealing the two major reasons for increased infectivity, The Lancet: The global pandemic is expected to end in March

    • Last Update: 2022-02-21
    • Source: Internet
    • Author: User
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    .

    A new paper published in Science published the world's first molecular-level analysis of the Omicron spike protein
    .

    The study, from the University of British Columbia School of Medicine, noted that Omicron has 37 mutations in the spike protein, 3-5 times more than previous new coronavirus variants
    .

    Further experiments also showed that the Omicron spike protein exhibited stronger antibody evasion—for all six of the monoclonal antibodies tested, and five of them were completely "evaded" by it
    .

    Corresponding author Sriram Subramaniam said: "Understanding the molecular structure of the virus's spike protein is critical for developing more effective treatments
    .

    Remarkably, despite so many mutations, Omicron has evolved to retain the ability to bind to human cells
    .

    For more research details, we refer to the paper in detail
    .

    The day after the most mutated variant was named by the WHO, researchers at the University of British Columbia quickly downloaded the genome sequence set posted online and sent a genetic sample of Omicron into the the laboratory
    .

    To figure out how the omicron variant attaches to and infects human cells, the researchers used cryo-electron microscopy to perform near-atomic-resolution structural analysis of the omicron binding to the human receptor ACE2
    .

    Among them, the "border" of the two (the black box in the above figure) is called the "Receptor Binding Domain" (RBD)
    .

    Electron microscopy results showed that Omicron was the most mutated variant of the new crown: a total of 37 spike protein mutations, 15 of which were present in the receptor binding domain
    .

    In contrast, the well-known delta has only 7 mutations compared to the originally isolated strain, and only 2 are present in the RBD region (in the S protein)
    .

    Regarding the spike protein: 1.
    It is the way that viruses adsorb and infect human cells; 2.
    The RBD region where the spike protein is located is also the main target of neutralizing antibodies
    .

    Most of the mutations that Omicron has in the RBD region are mutations that reduce the ability to bind to the human receptor ACE2 through high-throughput analysis
    .

    Nevertheless, compared with Delta, Omicron's affinity for human cells did not decrease, but remained at a comparable level
    .

    How is this going? Further observations revealed that there is a "compensatory mechanism" in Omicron, and three other mutations (R493, S496 and R498) created new salt bridges and hydrogen bonds between Omicron and the ACE2 receptor
    .

    These three "returned a game" after various mutations reduced the affinity level of Omicron
    .

    The researchers say this shows that, despite numerous mutations along the way, the new Omicron variant retains the ability to bind to human receptors
    .

    Next, the researchers conducted further experiments on the effect of the Omicron mutation on antibody neutralization
    .

    Sources of antibodies tested included: Monoclonal antibodies from sera obtained from 30 two-shot vaccinated individuals who had not been infected with Covid-19 Serum from 68 unvaccinated Covid-19 recoveries who had been infected with Alpha, SARS-CoV-2 variants such as Gamma or Delta were then subjected to neutralization experiments using pseudoviruses containing wild-type, delta, or Omicron S proteins to compare the ability of these pseudoviruses to evade antibodies
    .

    In experiments examining the effect of the omicron mutation on the "escape" of monoclonal antibodies, it was found that omicron was unable to fully neutralize five of the six tested antibodies
    .

    The only fully neutralized S309 antibody (yellow), although the neutralization ability did not decrease, the effect was also diminished
    .

    The researchers explained that this result may indicate that the unusually high number of mutations in the omicron spike protein gives it a stronger ability to escape antibodies compared to previous SARS-CoV-2 variants
    .

    For the current vaccine/immunity effect, the researchers also conducted experiments
    .

    The results showed that, compared with the wild type, the neutralization ability of the convalescent sera to the Omicron variant decreased to 1/6.
    3 on average, while the serum neutralization ability of the vaccinated population decreased to 1/4.
    4 of the original
    .

    Compared with the delta variant, the sera of convalescent patients showed a greater reduction in neutralization capacity (1/8.
    2), while the vaccinated group also showed a decrease in neutralization capacity, but to a lesser extent (1/3.
    4)
    .

    Despite showing greater antibody evasion, such experimental results suggest that the vaccine is still more effective against Omicron than the natural infection immunity developed by unvaccinated new crown patients
    .

    Corresponding author Subramaniam also emphasized: This shows that vaccines are still our best defense
    .

    To sum up briefly, at the molecular level, the study points to a number of mutations on the surface of the Omicron spike protein that are thought to help the virus evade antibodies elicited by vaccination or previous infection
    .

    And such widespread mutations did not affect Omicron's ability to bind to human cells
    .

    Although mutations such as K417N affected its binding efficiency to the ACE2 receptor, other novel mutations interacted to restore this binding ability
    .

    As the authors of the paper put it: From all these indications, Omicron seems to have been able to selectively strike a balance between the ability of antibodies to escape and the ability to bind to human cells
    .

    The research team of this paper is from the University of British Columbia (UBC) School of Medicine, and the corresponding author is Dr.
    Sriram Subramaniam, a professor in the UBC Department of Biochemistry and Molecular Biology
    .

    He is globally recognized for his leading contributions to cryo-EM
    .

    Google Scholar shows that its h-index is 66 and the total number of citations exceeds 15,000
    .

    One More Thing In addition, also recently, The Lancet, an authoritative medical journal, published an opinion article saying that with the rapid spread of Omicron, the global new crown pandemic is expected to end in March this year.

    .

    The author is Christopher Murray, director of the Institute for Health Metrics and Evaluation at the University of Washington
    .

    For the past two days, his team has been tasked with providing the White House with COVID-19 modeling
    .

    In his article, he stated that by March 2022, a large portion of the world will be infected with the Omicron variant
    .

    At the same time, as the vaccination rate continues to increase, the global immunization level will reach an all-time high
    .

    After that, while new coronavirus variants will still emerge, the pandemic should be contained
    .

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