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Original languageEnglish
Pages (from-to)2124-2133
JournalJournal of General Virology
Volume90
Issue9
DOIs
Publication statusPublished - Oct 2009

Abstract

The non-structural protein 1 (NS1) of the influenza A virus and the NS2 protein, which is also known as nuclear export protein, play important roles in the infectious life cycle of the virus. The objective of this study was to find the degree of conservation in the NS proteins and to identify conserved sites of functional or structural importance that may be utilized as potential drug target sites. The analysis was based on 2620 amino acid sequences for the NS1 protein and 1195 sequences for the NS2 protein. The degree of conservation and potential binding sites were mapped onto the protein structures obtained from a combination of experimentally available structure fragments with predicted threading models. In addition to high conservation in protein regions of known function, novel highly conserved sites have been identified, namely Glu159, Thr171, Val192, Arg200, Glu208 and Gln218 on the NS1 protein and Ser24, Leu28, Arg66, Arg84, Ser93, Ile97 and Leu103 on the NS2 protein. Using the Q-SiteFinder binding site prediction algorithm, several highly conserved binding sites were found, including two spatially close sites on the NS1 protein, which could be targeted with a bivalent ligand that would interfere with double-stranded RNA binding. Altogether, this work reveals novel universally conserved residues that are candidates for protein–protein interactions and provide the basis for designing universal anti-influenza drugs.

Notes

Original article can be found at: http://vir.sgmjournals.org/ Copyright Society for General Microbiology "This is an author manuscript that has been accepted for publication in Microbiology, copyright Society for General Microbiology, but has not been copy-edited, formatted or proofed. Cite this article as appearing in Microbiology. This version of the manuscript may not be duplicated or reproduced, other than for personal use or within the rule of 'Fair Use of Copyrighted Materials' (section 17, Title 17, US Code), without permission from the copyright owner, Society for General Microbiology. The Society for General Microbiology disclaims any responsibility or liability for errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final copy-edited, published article, which is the version of record, can be found at http://mic.sgmjournals.org, and is freely available without a subscription." DOI: 10.1099/vir.0.011270-0

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