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    Home > Active Ingredient News > Infection > Wu Zhiwei/Liu Yalan team jointly develops inhaled new nanoantibodies to effectively inhibit new coronavirus infections

    Wu Zhiwei/Liu Yalan team jointly develops inhaled new nanoantibodies to effectively inhibit new coronavirus infections

    • Last Update: 2021-11-05
    • Source: Internet
    • Author: User
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    Recent popular reports from Yimaike ★ Roche and CombiGene signed an agreement to develop AAV gene therapy for the treatment of drug-resistant epilepsy Yimai Meng broke the news ★ "Father of CAR-T" Professor Carl June joins Beiheng Biosciences Advisory Team October 2021 March 19/eMedClub News/--Since the outbreak of the new crown epidemic in December 2019, the cumulative number of infections worldwide has exceeded 235 million, and the death toll has exceeded 4.
    8 million
    .

    Although various vaccines have been widely promoted, they still have not been able to prevent the outbreak of the new crown epidemic
    .

    What’s more serious is that with the development of the epidemic, the new crown virus is also continuing to mutate.
    At present, 90% of the main epidemic strains in Europe, North America and Asia are Delta (Delta) strains.
    Recently, Nanjing, Yangzhou, The COVID-19 outbreak in Fujian and Harbin was also caused by the Delta strain
    .

    Up to now, there is no clinically relevant specific drugs, and most of the antibody drugs developed in the early stage have lost antiviral activity against the Delta strain.
    Therefore, new antibody drugs are urgently needed to be developed
    .

    On the other hand, new coronavirus infections are mainly concentrated in the lungs and nasopharynx.
    Conventional antibodies are administered intravenously, and only 0.
    2% of them can reach the lungs, and basically cannot reach the nasopharynx.
    Because of this, the current clinical application of antibody medications The dose required for the new crown is very large, and even so, the clinical efficacy is still not significant, so new methods of administration need to be tried
    .

    Borrowing from the previous work foundations of the research and development of high-throughput nanoantibodies against viral infections (Xilin Wu, et al.
    , JCI Insight, 2020) and the development of single-gene dual-targeted antibodies (Xilin Wu, et al.
    , JCI, 2018), Professor Wu Zhiwei’s team has developed a new type of dual-targeting nanobody Nb15, which can effectively inhibit Alpha, Epsilon, Delta and other new coronavirus epidemic strains, while also inhibiting 94.
    7% (18/19) of the single For point mutants, the average IC50 is as low as 0.
    8 ng/ml (10 pM)
    .

    Experimental results show that Nb15 has a high-efficiency and broad-spectrum anti-coronavirus effect, and its IC50 value ranks in the forefront of the novel coronavirus antibodies that have been published so far
    .

    At the same time, in order to further improve the broad-spectrum and half-life of Nb15, Professor Wu Zhiwei’s team has constructed a new dual-targeting nanobody Nb15-NbH-Nb15, which has the unique thermal stability of nanobodies, with a temperature of 70 oC.
    The hourly activity still retains 100% activity.
    In addition, Nb15-NbH-Nb15 has high-efficiency and broad-spectrum anti-coronavirus (including Delta strain) activity
    .

    In order to verify whether the new dual-targeting nano can treat the new coronavirus infection, we conducted in vivo experiments in mice.
    The results showed that Nb15-NbH-Nb15 can significantly inhibit the infection of humanized mice with the new coronavirus after inhalation administration of Nb15-NbH-Nb15
    .

    The completion of the project is expected to provide a portable, low-cost new type of inhaled nanobody drug for the fight against new crown infections, which is clinically important for the treatment of breakthrough infections that are currently raging around the world after delta virus vaccination.
    Meaning
    .

    Figure 1 The construction and identification of dual-targeting nanobody The project has the following highlights: 1) The completion of the research and development of the new trimeric dual-targeting nanobody NbX1-NbH-NbX2 (Nb15-NbH-Nb15) provides a kind of nanobody New construction form
    .

    2) Nb15-NbH-Nb15 can improve the antiviral activity of Nb15, and at the same time can greatly extend the half-life of Nanobodies in vivo
    .

    3) Nb15-NbH-Nb15 can effectively neutralize new coronavirus infections including delta, with an IC50 of pM, which is comparable to the antiviral activity of the best neutralizing antibody that has been reported
    .

    4) Through inhaled administration, Nb15-NbH-Nb15 can effectively prevent or treat neocoronavirus infection in hACE2 mice
    .

     Figure 2 Schematic diagram of the development of inhaled new dual-targeting nanobody Journal) (https://
    .

    Associate researcher Wu Xilin from Nanjing University School of Medicine, Dr.
    Fu Ming from Wuhan Institute of Virology, etc.
    are the first authors of the paper.
    Professor Wu Zhiwei from Nanjing University School of Medicine and Associate Researcher Liu Yalan from Wuhan Institute of Virology, Chinese Academy of Sciences are the corresponding authors
    .

    The research was supported by the National Natural Science Foundation of China, the “Thirteenth Five-Year Infectious Diseases Major Special Project” fund, the six talent peaks of Jiangsu Province, and the Jiangsu Shuangchuang Ph.
    D.
    program
    .


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