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    Home > Active Ingredient News > Infection > "Science" publishes a Chinese team paper, providing new ideas for the design and development of broad-spectrum anti-COVID-19 antibodies

    "Science" publishes a Chinese team paper, providing new ideas for the design and development of broad-spectrum anti-COVID-19 antibodies

    • Last Update: 2022-03-08
    • Source: Internet
    • Author: User
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    ▎The main content of this article comes from the Jimin Trust press release On February 8, 2022, the journal Science published online the collaboration between the team of Professor Xu Huaqiang/Dr.
    Yin Wanchao from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences and the team of Dr.
    The latest work titled "Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody"
    .

    This study analyzed the high-resolution cryo-electron microscopy structure of the Omicron spike protein binding to the human receptor ACE2 and the broad-spectrum anti-COVID-19 antibody JMB2002 complex, expounded the molecular mechanism of the rapid spread and immune escape of Omicron mutants, and revealed the therapeutic antibody JMB2002 The new mechanism of action provides new ideas for the design and development of broad-spectrum anti-COVID-19 antibodies
    .

    The researchers found that the Omicron spike protein binds to its receptor ACE2 nearly 6 times higher than that of the wild type.
    It was observed from the structure that the adjacent RBDs of the Omicron spike protein trimer interacted to form an RBD dimer (Fig.
    1B), which was conducive to the continuous open state of the RBD of the Omicron spike protein and enhanced the infection of the Omicron mutant strain.
    Combined with thermodynamic experiments, it was found that the RBD of the Omicron spike protein is highly flexible and unstable, and its thermal dissolution temperature dropped by more than 5 °C (Fig.
    1C), making the spike protein easier to switch from the closed conformation to the open conformation, further Enhanced infectivity of Omicron variants
    .

    In short, the interaction and instability of the Omicron spike protein RBD, which promotes the interaction of the Omicron spike protein with ACE2, explains the underlying mechanism of the enhanced infectivity of Omicron mutant strains at the atomic level
    .

    ▲Figure 1 The structure of the Omicron spike protein bound to the human receptor ACE2
    .

    A shows the overall conformation of the Omicron spike protein bound to human ACE2 structure, B shows the RBD-RBD dimer, and the interaction interface of RBD binding to ACE2, and C shows the thermal stabilization result of the spike protein
    .

    (Image source: Reference [1]) It can be seen from the resolved structure that many mutation sites of the Omicron spike protein are located on the surface of the protein, causing most of the neutralizing antibodies to lose their neutralizing activity against Omicron mutant strains
    .

    Fortunately, the new crown neutralizing antibody JMB2002 independently developed by Jimin Trust has an affinity for Omicron spike protein 4 times that of the wild type, showing a strong potential to inhibit Omicron mutants
    .

    In order to clarify the molecular mechanism of JMB2002 resistance to Omicron mutants, the researchers analyzed the structure of the Omicron spike protein complex with JMB2002 (Figure 2A-C).
    Figure 2D), the binding of JMB2002 antibody to Omicron spike protein RBD blocked the binding of human receptor protein ACE2 to RBD (Figure 2E); surprisingly, JMB2002 bound at the RBD-human ACE binding interface in a new conformation On the back, is a novel epitope-binding neutralizing antibody (Figure 2F)
    .

    ▲Figure 2 The structure of the Omicron spike protein-binding antibody JMB2002
    .

    A shows the overall structure of JMB2002 antibody bound to Omicron spike protein, B shows the conformation of Omicron spike protein in complex, C shows the structure comparison of two RBDs bound to JMB2002 antibody, D shows the structure of JMB2002 antibody bound to Omicron spike protein The dimer of RBD-RBD, E shows that JMB2002 antibody binds to Omicron's RBD and blocks further binding of ACE2, F is the classification of anti-new coronavirus neutralizing antibodies, and JMB2002 antibody is a new type of antibody, which is classified into the fifth category
    .

    (Image source: Reference [1]) At the time of the pandemic of the new coronavirus variant Omicron, the research results are original and novel.
    The paper has been peer-reviewed and published in "Science", which will help global researchers to fully Understanding the characteristics of the Omicron variant provides new ideas for the development of broad-spectrum anti-COVID-19 antibodies, as well as new references for the global COVID-19 vaccine development
    .

    Researcher Yin Wanchao of Shanghai Institute of Materia Medica, assistant researcher Dr.
    Xu Youwei and Dr.
    Xu Peiyu, and postdoctoral fellow Wu Canrong, together with Jimin Xinxin Dr.
    Cao Xiaodan and Dr.
    Gu Chunyin are the co-first authors of the paper
    .

    Professor Xu Huaqiang, Researcher Yin Wanchao, and Dr.
    Deng Sujun of Jimin Xinxin from Shanghai Institute of Materia Medica are the co-corresponding authors of this paper
    .

    Reference: [1] Wanchao Yin et al.
    , Structures of the Omicron Spike trimer with ACE2 and an anti-Omicron antibody, Science (2022).
    DOI: 10.
    1126/science.
    abn8863
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