國家衛生研究院 NHRI:Item 3990099045/1175
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    题名: Antiviral activity of pyridyl imidazolidinones against enterovirus 71 variants
    作者: Chen, TC;Liu, SC;Huang, PN;Chang, HY;Chern, JH;Shih, SR
    贡献者: Division of Biotechnology and Pharmaceutical Research
    摘要: Pyridyl imidazolidinone is a novel class of capsid binder which can inhibit enterovirus 71 (EV71). In this study, we tested the susceptibility of six recombinant viruses with different single-site mutations in VP1. Eleven modified pyridyl imidazolidinones were synthesized and used to probe the interaction between these compounds and the EV71 VP1 protein. We found that the D31N or E98K mutant viruses were susceptible to bulkier compounds, which suggested that mutations at these two sites in VP1 may widen the hydrophobic pocket of VP1, allowing bulkier compounds to enter and interfere VP1-receptor binding. Additionally, the Y116H mutant was more resistant to pyridyl imidazolidinone compounds containing a methyl group in the central position of the hydrophobic linker. When a trifluoromethyl group was substituted for the methyl group in the middle of the linker chain, the inhibitory effect was totally abolished in the Y116H mutant, suggesting that the interaction between Tyr (Y) 116 of VP1 and the central position of the linker chain of pyridyl imidazolodinone is very important for drug efficacy. A V192M mutant was resistant to most of the derivatives, indicating that residue 192 is a key mutation for resistance to pyridyl imidazolidinone.
    关键词: Medicine, Research & Experimental
    日期: 2008-05
    關聯: Journal of Biomedical Science. 2008 May;15(3):291-300.
    Link to: http://dx.doi.org/10.1007/s11373-007-9228-5
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-7770&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000255092500002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=42449163412
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