國家衛生研究院 NHRI:Item 3990099045/9548

NHRI > Institute of Biotechnology and Pharmaceutical Research > John Tsu-An Hsu > Periodical Articles > Item 3990099045/9548

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9548

Title:	Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development
Authors:	Liu, CL;Hung, HC;Lo, SC;Chiang, CH;Chen, IJ;Hsu, JT;Hou, MH
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus-infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP's RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus.
Date:	2016-02-26
Relation:	Scientific Reports. 2016 Feb 26;6:Article number 21662.
Link to:	http://dx.doi.org/10.1038/srep21662
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-2322&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000370858100001
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84959431668
Appears in Collections:	[John Tsu-An Hsu] Periodical Articles

Files in This Item:

File	Description	Size	Format
PUB26916998.pdf		1788Kb	Adobe PDF	643	View/Open

Loading...