國家衛生研究院 NHRI:Item 3990099045/5970

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Title:	Identification of BPR3P0128 as an Inhibitor of cap-snatching activities of influenza virus
Authors:	Hsu, JT;Yeh, JY;Lin, TJ;Li, ML;Wu, MS;Hsieh, CF;Chou, YC;Tang, WF;Lau, KS;Hung, HC;Fang, MY;Ko, S;Hsieh, HP;Horng, JT
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	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. The 50% inhibitory concentrations were in the range of 51-190 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 complementary RNA 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 cellular factor(s) associated with viral PB2 cap-snatching activity. The identification of these factor(s) could help redefine the regulation of viral transcription and replication, and thereby provide a potential target for antiviral chemotherapeutics.
Date:	2012-02
Relation:	Antimicrobial Agents and Chemotherapy. 2012 Feb;56(2):647-657.
Link to:	http://dx.doi.org/10.1128/aac.00125-11
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:000299658900007
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84862908885
Appears in Collections:	[John Tsu-An Hsu] Periodical Articles [Hsing-Pang Hsieh] Periodical Articles

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