國家衛生研究院 NHRI:Item 3990099045/1246
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    题名: Mutation in enterovirus 71 capsid protein VP1 confers resistance to the inhibitory effects of pyridyl imidazolidinone
    作者: Shih, SR;Tsai, MC;Tseng, SN;Won, KF;Shia, KS;Li, WT;Chern, JH;Chen, GW;Lee, CC;Lee, YC;Peng, KC;Chao, YS
    贡献者: Division of Biotechnology and Pharmaceutical Research;Division of Biostatistics and Bioinformatics
    摘要: Enterovirus 71 is one of the most important pathogens in the family of Picornaviridae that can cause severe complications in the postpoliovirus era, such as encephalitis, pulmonary edema, and even death. Pyridyl imidazolidinone is a novel class of potent and selective human enterovirus 71 inhibitor. Pyridyl imidazolidinone was identified by using computer-assisted drug design. This virologic investigation demonstrates that BPR0-194, one of the pyridyl imidazolidinones, targets enterovirus 71 capsid protein VP1. Time course experiments revealed that BPR0Z-194 effectively inhibited virus replication in the early stages, implying that the compound can inhibit viral adsorption and/or viral RNA uncoating. BPR0Z-194 was used to select and characterize the drug-resistant viruses. Sequence analysis of the VP1 region showed that the resistant variants differed consistently by seven amino acids in VP1 region from their parental drug-sensitive strains. Site-directed mutagenesis of enterovirus 71 infectious cDNA revealed that a single amino acid alteration at the position 192 of VP1 can confer resistance to the inhibitory effects of BPR0Z-194.
    关键词: Microbiology;Pharmacology & Pharmacy
    日期: 2004-09
    關聯: Antimicrobial Agents and Chemotherapy. 2004 Sep;48(9):3523-3529.
    Link to: http://dx.doi.org/10.1128/AAC.48.9.3523-3529.2004
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0066-4804&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000223625800045
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=4344601173
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