標題: Identification of BPR3P0128 as an Inhibitor of Cap-Snatching Activities of Influenza Virus
作者: Hsu, John T. -A.
Yeh, Jiann-Yih
Lin, Ta-Jen
Li, Mei-ling
Wu, Ming-Sian
Hsieh, Chung-Fan
Chou, Yao Chieh
Tang, Wen-Fang
Lau, Kean Seng
Hung, Hui-Chen
Fang, Ming-Yu
Ko, Shengkai
Hsieh, Hsing-Pang
Horng, Jim-Tong
生物科技學系
Department of Biological Science and Technology
公開日期: 1-二月-2012
摘要: The aim of this study was to identify the antiviral mechanism of a novel compound, BPR3P0128. From a large-scale screening of a library of small compounds, BPR3P compounds were found to be potent inhibitors of influenza viral replication in Madin-Darby canine kidney (MDCK) cells. BPR3P0128 exhibited inhibitory activity against both influenza A and B viruses. The 50% inhibitory concentrations were in the range of 51 to 190 nM in MDCK cells, as measured by inhibition-of-cytopathic-effect assays. BPR3P0128 appeared to target the viral replication cycle but had no effect on viral adsorption. The inhibition of cap-dependent mRNA transcription by BPR3P0128 was more prominent with a concurrent increase in cap-independent cRNA replication in a primer extension assay, suggesting a role of BPR3P0128 in switching transcription to replication. This reduction in mRNA expression resulted from the BPR3P-mediated inhibition of the cap-dependent endoribonuclease (cap-snatching) activities of nuclear extracts containing the influenza virus polymerase complex. No inhibition of binding of 5' viral RNA to the viral polymerase complex by this compound was detected. BPR3P0128 also effectively inhibited other RNA viruses, such as enterovirus 71 and human rhinovirus, but not DNA viruses, suggesting that BPR3P0128 targets a cellular factor(s) associated with viral PB2 cap-snatching activity. The identification of this factor(s) could help redefine the regulation of viral transcription and replication and thereby provide a potential target for antiviral chemotherapeutics.
URI: http://dx.doi.org/10.1128/AAC.00125-11
http://hdl.handle.net/11536/15230
ISSN: 0066-4804
DOI: 10.1128/AAC.00125-11
期刊: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume: 56
Issue: 2
起始頁: 647
結束頁: 657
顯示於類別:期刊論文


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  1. 000299658900007.pdf