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    Home > Active Ingredient News > Drugs Articles > The Chinese team's work was named science cover today: discovering new anti-new coronavirus candidates.

    The Chinese team's work was named science cover today: discovering new anti-new coronavirus candidates.

    • Last Update: 2020-07-20
    • Source: Internet
    • Author: User
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    Today, the cover of Science magazine covers an important study from a Chinese research team - Liu Hong/Xu Yechun/Jiang Hualiang of the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences,

    , and the team of Yang Haitao/Rao Zi and the team of The Wuhan Virus Institute of the Chinese Academy of Sciences, Zhang Lei /Xiao Weifu, have made important progress in the study of anti-new coronavirus drugs and found a new, efficient and safe anti-SARS-CoV-2 virus candidate drug

    Photo Source: Illustration Illustration; C

    Bickel/Science; Data: PDB ID 6M0K (SARS-CoV-2 main protease)

    the study was originally published on The BioRxiv



    biopreprinted on March 28 and published online April 22 in Science

    Today's cover of Science also proves the importance of the job

    In this article, we revisit the key information of this study
    the following rereproduced from the "Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences"

    SCIENCE , Liu Hong / Yang Haitao / Xu Yechun / Zhang Lei team based on structural drug design strategy to develop a new anti-SARS-CoV-2 virus candidate

    recently,

    the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences Liu Hong / Xu Yechun/Jiang Hualiang team in conjunction with Shanghai University of Science and Technology Yang Haitao / Rao Zi and the team and the Chinese Academy of Sciences Wuhan Virus Institute Zhang Lei / Xiao Weifu team to make important progress in anti-new coronavirus drug research, the discovery of a new structure, efficient and safe anti-SARS-CoV-2 virus candidate drugs

    published the findings on the bio-Rxiv

    ,

    , on The Bio-Preprinted website, on March 28 and published online April 22 at the

    Science





    To date, pneumonia (COVID-19) caused by the new coronavirus (SARS-CoV-2) infection has reached 2.5 million confirmed cases worldwide, the number of infection deaths has increased to 170,000, has developed into a global pandemic, and there are currently no specific antiviral drugs and vaccines for THE treatment of COVID-19



    SARS-CoV-2 is a single positive chain RNA virus, and SARS-CoV and MERS-CoV have a higher homologous

    After the virus infection enters the host cell, with the help of the host cell, its genetic material RNA first translates to express two polyprotein precursors (pp1a and pp1ab), the polymer precursor under the action of 3CL protease and papaya-like protease in the molecule slicing produces multiple non-structural proteins, because 3CL protease is responsible for at least 11 site cutting, so the main gene protein asse (main protease, Mpro)

    Non-structural proteins produced by polyprotein precursors are involved in the production of viral subgene RNA and four structural proteins (E protein, M protein, S protein and N protein) to complete the reproduction and release of sub-viruses

    Because the main protease plays a vital role in the life cycle of the virus and there is no homologous protein in the human body, the main protease is an ideal target for the development of antiviral drugs

    Liu Hong/Jiang Hualiang team has been engaged in antiviral drug research and development for many years and has accumulated a wealth of experience

    Based on the three-dimensional structure of the coronavirus main protease, the team designed and synthesized two peptide compounds 11a and 11b

    Both compounds showed excellent inhibitory activity in vitro for SARS-CoV-2 Mpro (11a: IC50 s 0.053 s 0.005 sm, 11b: IC50 s 0.040 s 0.002 m M), while antiviral activity testresults showed that compounds 11a and 11b had better antiviral effects, with EC5000.53 and M

    More important
    both compounds demonstrate good pharmacokinetic properties and safety in the body and have the potential to develop new drugs to fight SARS-CoV-2



    The three-dimensional structure of the

    compounds 11a and 11b and the main protease complex of the SARS-CoV-2 main protease inhibitors and the chemical structure of the compounds 11a and 11b (photo source: References) shows that both compounds occupy the substrate binding pocket, wherein the compound's aldehyde-based and protease catalytic senosis are firmly formed at the 145-bit nucleus

    The highly distinguished compound structure information not only shows the precise interaction patterns of compounds 11a and 11b and main protease, but also reveals the molecular mechanism of compound inhibition of viral proteases



    Figure 2 Compounds 11a and 11b and SARS-CoV-2 main protease crystal complex and binding model (Photo source: References)

    Liu Hong Researcher of Shanghai Institute of Drug Research of the Chinese Academy of Sciences, Professor Yang Haitao of Shanghai University of Science and Technology, Zhang Lei of the Wuhan Virus Institute of the Chinese Academy of Sciences, and Xu Yechun Researcher of the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences

    Among them, Liu Hong/Xu Yechun/Jiang Hualiang team completed the evaluation of compound design, synthesis and enzyme level inhibition activity, Zhang Lei /Xiao Yufu team completed the cell level antiviral activity assessment, Yang Haitao/Rao Zi and the team completed the analysis of the crystal structure of compounds and target protein compounds

    The study was also supported by the National Center for The Evaluation of Safety of New Drugs in Chengdu

    the Shanghai Institute of Medicine of the Chinese Academy of Sciences and the Chinese University of Pharmaceutical Sciences jointly trained doctoral student Dai Wenhao, Shanghai University of Science and Technology Institute of Immunochemistry Associate Researcher Dr

    Zhang Bing, Wuhan Virus Research Institute master's student Jiang Xiaming and the Chinese Academy of Sciences Shanghai Institute of Medicine doctoral student Su Haixia as co-first authors of this article

    the research was supported by the Ministry of Science and Technology of the State, the National Natural Science Foundation of China, the China Academy of Engineering-Ma Yun Foundation, the Shanghai Science and Technology Commission, the Guangxi Zhuang Autonomous Region Science and Technology Office and Frontier Biopharmaceuticals (Nanjing) Co., Ltd

    full text link:

    References:





    (2020), Structure-based design of antiviral drug targeting the SARS-CoV-2 main protease, Science, DOI: 10.1126/science.abb4489


    from



    SCIENCE, Liu Hong/Yang Haitao/Xu Yechun/Zhang Lei, a team of developed a new anti-Co-Virus-2 drug based on a structured drug design strategy. 
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