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  1. Article ; Online: Bepridil is potent against SARS-CoV-2 in vitro.

    Vatansever, Erol C / Yang, Kai S / Drelich, Aleksandra K / Kratch, Kaci C / Cho, Chia-Chuan / Kempaiah, Kempaiah Rayavara / Hsu, Jason C / Mellott, Drake M / Xu, Shiqing / Tseng, Chien-Te K / Liu, Wenshe Ray

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 10

    Abstract: Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS- ... ...

    Abstract Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M
    MeSH term(s) A549 Cells ; Animals ; Antiviral Agents/pharmacology ; Bepridil/pharmacology ; Chlorocebus aethiops ; Drug Discovery ; Humans ; Molecular Docking Simulation ; Molecular Structure ; SARS-CoV-2/drug effects ; Small Molecule Libraries ; Vero Cells
    Chemical Substances Antiviral Agents ; Small Molecule Libraries ; Bepridil (755BO701MA)
    Language English
    Publishing date 2021-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2012201118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD.

    Ma, Hang / Guo, Yingying / Tang, Haoneng / Tseng, Chien-Te K / Wang, Lei / Zong, Huifang / Wang, Zhenyu / He, Yang / Chang, Yunsong / Wang, Shusheng / Huang, Haiqiu / Ke, Yong / Yuan, Yunsheng / Wu, Mingyuan / Zhang, Yuanyuan / Drelich, Aleksandra / Kempaiah, Kempaiah Rayavara / Peng, Bi-Hung / Wang, Ailin /
    Yang, Kaiyong / Yin, Haiyang / Liu, Junjun / Yue, Yali / Xu, Wenbo / Zhu, Shuangli / Ji, Tianjiao / Zhang, Xiaoju / Wang, Ziqi / Li, Gang / Liu, Guangchun / Song, Jingjing / Mu, Lingling / Xiang, ZongShang / Song, Zhangyi / Chen, Hua / Bian, Yanlin / Zhang, Baohong / Chen, Hui / Zhang, Jiawei / Liao, Yunji / Zhang, Li / Yang, Li / Chen, Yi / Gilly, John / Xiao, Xiaodong / Han, Lei / Jiang, Hua / Xie, Yueqing / Zhou, Qiang / Zhu, Jianwei

    Cell discovery

    2022  Volume 8, Issue 1, Page(s) 16

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.
    Language English
    Publishing date 2022-02-15
    Publishing country England
    Document type Journal Article
    ISSN 2056-5968
    ISSN 2056-5968
    DOI 10.1038/s41421-022-00381-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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