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    Home > Active Ingredient News > Infection > Professor Zhu Jianwei's team from Cell Discovery Jiaotong University discovered a broad-spectrum neutralizing antibody against COVID-19, and has obtained IND approval for a broad-spectrum neutralizing antibody against RS-CoV-2

    Professor Zhu Jianwei's team from Cell Discovery Jiaotong University discovered a broad-spectrum neutralizing antibody against COVID-19, and has obtained IND approval for a broad-spectrum neutralizing antibody against RS-CoV-2

    • Last Update: 2022-03-06
    • Source: Internet
    • Author: User
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    This article is reproduced from the School of Pharmacy, Shanghai Jiao Tong University.
    Since the first positive case of COVID-19 was confirmed at the end of 2019, the SARS-CoV-2 virus has caused more than 400 million infections worldwide
    .

    The spike (S) protein of the SARS-CoV-2 virus mediates the binding of the virus to the ACE2 receptor on the surface of the host cell, which is an ideal target for the development of anti-SARS-CoV-2 virus antibody drugs
    .

    The key region where the S protein binds to ACE2 is called the RBD region.
    Using neutralizing antibodies to block the binding of RBD to ACE2 can effectively prevent SARS-CoV-2 virus infection
    .

    However, since SARS-CoV-2 is a single-chain virus that is very susceptible to mutation, and many mutant strains have been produced, the broad neutralizing ability of antibodies is also an important consideration
    .

    After the outbreak of the new crown epidemic, the team of Professor Zhu Jianwei of the Engineering Research Center for Cell Engineering and Antibody Drugs of the Ministry of Education cooperated with many domestic and foreign enterprises and institutions to clone and screen from the B cells of recovered patients.
    Potent neutralizing antibody
    .

    After a series of in vivo and in vitro activity evaluation, antibody mechanism study, structure analysis, safety evaluation, druggability evaluation and production process development, the team successfully obtained the most valuable candidate antibody 2G1, which has been obtained Clinical approval
    .

    The related results were recently published in the famous journal Cell Discovery (2021 impact factor is about 32.
    4)
    .

    The study first collected blood samples from patients who had recovered from the new crown, isolated memory B cells from them, and then cloned hundreds of IgG antibody molecules
    .

    Through a series of binding ability screening and pseudovirus neutralization experiments, dozens of candidate antibodies were finally obtained (Figure 1)
    .

    Among these candidate antibodies, 2G1 exhibited the strongest neutralizing activity, so it was further evaluated
    .

    Figure 1.
    SARS-CoV-2 neutralizing antibody development process The research team then explored the effects of some major mutation sites and major mutant strains on the activity of antibody 2G1, and found mutation sites such as N439K, Y453F, E484K and N501Y as well as Alpha, Concerning strains such as Beta, Gamma, and Delta did not significantly affect 2G1 activity (Figure 2)
    .

    Antibody 2G1 has nanomolar affinity to the main mutant strain
    .

    This indicates that the antibody 2G1 has good anti-mutation ability and broad neutralizing ability against SARS-CoV-2
    .

    Figure 2.
    Evaluation of Anti-mutation Ability of Antibody 2G1 This study evaluated the in vivo activity of antibody 2G1 using both a transgenic mouse model and a rhesus macaque model
    .

    In transgenic mouse experiments, 2G1 at doses of 20, 6.
    7, or 2.
    2 mg/kg completely protected mice from WA1/2020 and Beta strains, and 2G1 protected mice from Delta strains.
    The dose is between 6.
    7 - 20 mg/kg
    .

    Experiments based on rhesus monkeys also yielded similar results, which further affirms the efficient neutralization ability of 2G1
    .

    The structural analysis results of cryo-electron microscopy showed that the antibody 2G1 bound to the tip region of the S protein trimer through extensive hydrophobic interactions, and the binding area to the S protein was very small, avoiding most of the mutation sites.
    The reason for the resistance to mutagenesis (Fig.
    3)
    .

    The combination of multiple antibodies is an effective means to fight against the mutation of SARS-CoV-2 virus.
    The small contact area makes 2G1 not easily conflict with other antibodies, so it has a high combined value
    .

    Figure 3.
    Epitope analysis of antibody 2G1 In this study, a series of valuable SARS-CoV-2 neutralizing antibodies were screened through B cell cloning technology, which is of great significance for the treatment of new crown infection and the control of new crown epidemic
    .

    The first corresponding author of the article is Professor Zhu Jianwei from the School of Pharmacy, Shanghai Jiao Tong University, and Ph.
    D.
    students Ma Hang and Tang Haoneng are the co-first authors
    .

    Professor Zhou Qiang of West Lake University and other collaborators provided help for the research
    .

    Full text link: https://
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