國家衛生研究院 NHRI:Item 3990099045/1111
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/1111


    Title: Structure-based drug design and structural biology study of novel nonpeptide inhibitors of severe acute respiratory syndrome coronavirus main protease
    Authors: Lu, IL;Mahindroo, N;Liang, PH;Peng, YH;Kuo, CJ;Tsai, KC;Hsieh, HP;Chao, YS;Wu, SY
    Contributors: Division of Biotechnology and Pharmaceutical Research
    Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) main protease (Mpro), a protein required for the maturation of SARS-CoV, is vital for its life cycle, making it an attractive target for structure-based drug design of anti-SARS drugs. The structure-based virtual screening of a chemical database containing 58 855 compounds followed by the testing of potential compounds for SARS-CoV Mpro inhibition leads to two hit compounds. The core structures of these two hits, defined by the docking study, are used for further analogue search. Twenty-one analogues derived from these two hits exhibited IC50 values below 50 mu M, with the most potent one showing 0.3 AM. Furthermore, the complex structures of two potent inhibitors with SARS-CoV Mpro were solved by X-ray crystallography. They bind to the protein in a distinct manner compared to all published SARS-CoV Mpro complex structures. They inhibit SARS-CoV Mpro activity via intensive H-bond network and hydrophobic interactions, without the formation of a covalent bond. Interestingly, the most potent inhibitor induces protein conformational changes, and the inhibition mechanisms, particularly the disruption of catalytic dyad (His41 and Cys145), are elaborated.
    Keywords: Chemistry, Medicinal
    Date: 2006-08-24
    Relation: Journal of Medicinal Chemistry. 2006 Aug;49(17):5154-5161.
    Link to: http://dx.doi.org/10.1021/jm060207o
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000239818200012
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33747458480
    Appears in Collections:[Su-Ying Wu] Periodical Articles
    [Hsing-Pang Hsieh] Periodical Articles
    [Yu-Sheng Chao(2002-2013)] Periodical Articles

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