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    Home > Active Ingredient News > Drugs Articles > The first release of the Chinese Academy of Sciences Xu Huaqiang/Yin Wanchao team to jointly tackle the new coronavirus Omicron mutant strain spike protein and its complex structure with receptors and antiviral antibodies

    The first release of the Chinese Academy of Sciences Xu Huaqiang/Yin Wanchao team to jointly tackle the new coronavirus Omicron mutant strain spike protein and its complex structure with receptors and antiviral antibodies

    • Last Update: 2022-01-09
    • Source: Internet
    • Author: User
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    It has been 2 years since the outbreak of the new crown epidemic.
    The number of confirmed cases worldwide has exceeded 280 million, and the death toll has exceeded 5.
    4 million

    .
    What is more worrying is that the new coronavirus has evolved a variety of "worrying mutant strains", which continue to bring uncertainty and new challenges to the global epidemic prevention and control, especially the latest Omicron mutant strains, The global raging has caused a new round of infection peaks

    .
    Statistics show that there are nearly 1 million new infections every day, and about 80% of the infections are caused by the Omicron mutant strain

    .

    The number of mutation sites of the new coronavirus Omicron mutant strain is significantly more than that of all new coronavirus mutants that have been circulating in the past two years, especially in the virus spike protein mutations as many as 37
    .
    At present, it is not clear how these mutations affect the infectivity of Omicron mutant strains and the mechanism that leads to immune escape

    .
    Recent studies have shown that more than 80% of the neutralizing antibodies against the new coronavirus are currently ineffective against Omicron mutants, or their effectiveness is significantly reduced.
    Therefore, we have a deep understanding of the molecular mechanism of the transmission and infection of Omicron mutants and developed specifics for Omicron mutants.
    Sex therapy antibodies are imminent

    .

    Figure 1 The structure of the Omicron mutant new coronavirus spike protein binding receptor ACE2
    .
    A shows the structure and conformation, B is the interaction interface of RBD and ACE2, and C is the interaction interface of RBD dimer

    .

    The team of Xu Huaqiang and Yin Wanchao of Shanghai Institute of Materia Medica, Chinese Academy of Sciences urgently tackled the problem and quickly resolved the Omicron mutant spike protein and the high-resolution cryo-EM structure that binds to the human receptor ACE2 in less than one month (Figures 1A and 1B)
    .
    The biochemical level binding showed that the receptor-binding domain (RBD) of the Omicron mutant strain’s receptor-binding domain (RBD) binding to the receptor ACE2 was significantly enhanced compared to the wild-type, which was probably increased by nearly 10 times; thermodynamic experiments showed that, The RBD of the Omicron mutant strain is highly flexible and unstable, which makes it easier for the spike protein to switch from a closed conformation to an open conformation.
    At the same time, we have observed from the analyzed structure that the adjacent RBD in the trimer of the Omicron mutant spike protein is specific Interaction, the formation of RBD dimers (Figure 1C), can stabilize the Omicron mutants’ spike protein specific RBDs in an open state.
    The instability of these Omicron mutants’ spike protein RBDs and their interactions make It is easier for the spike protein of the Omicron mutant strain to interact with the receptor ACE2, which explains the increased infectivity of the Omicron mutant from the atomic level

    .
    At the same time, the structure we analyzed shows that most of the mutation sites of the Omicron variant spike protein are located on the surface of the protein, including multiple epitopes.
    This structurally explains the molecular mechanism of the Omicron variant strain against most neutralizing antibodies.

    .
    On the basis of this work, the team of Xu Huaqiang and Yin Wanchao of Shanghai Institute of Materia Medica, Chinese Academy of Sciences, combined with the team of Jimin Credible Deng Sujun, conquered the structure of the Omicron variant spike protein and the specific therapeutic antibody JMB2002 (Figure 2A-D)

    .
    The antibody has completed a phase 1 clinical trial, and has a strong therapeutic effect and high safety

    .
    Biochemical level binding experiments show that the binding power of the antibody to the spike protein of the Omicron mutant strain is 4 times that of the wild-type, showing a strong potential to inhibit the Omicron mutant strain

    .
    From the structure of the complex obtained from the analysis, we found that the JMB2002 antibody fragment binds to the back of the RBD receptor binding motif in a new conformation, which is an antibody with a new mechanism of action (Figure 2E)

    .
    Combined with biochemical and antiviral neutralization experiments, we elaborated that the antibody JMB2002 has a broad-spectrum molecular mechanism against the new coronavirus

    .
    The cryo-electron microscopy data in this study was collected on the Shanghai Gaofeng Talents cryo-electron microscopy platform

    .
    This work was funded by the Shanghai Talent Summit Program, the National Natural Science Foundation of China, the National Health Commission's major science and technology projects, the national key basic research plan, and the Shanghai major science and technology projects

    .

    Figure 2 The structure of the Omicron mutant new coronavirus spike protein binding antibody JMB2002
    .
    A shows the binding of JMB2002 antibody fragment to the Omicron mutant and wild-type new coronavirus spike protein, B shows the inhibition of the JMB2002 antibody on the Omicron mutant and wild-type, respectively, and C is the Omicron mutant new coronavirus spike protein binding antibody JMB2002 Structure, D is the structural comparison of RBD binding to JMB2002 antibody fragment, E is the classification of neutralizing antibodies against the new coronavirus, and JMB2002 antibody is a new type of antibody and is classified as the fifth category

    .

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