University of Hertfordshire


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Original languageEnglish
Pages (from-to)112-120
Number of pages9
Early online date17 Jun 2017
Publication statusPublished - 1 Sep 2017


The influenza A basic polymerase protein 2 (PB2) functions as part of a heterotrimer to replicate the viral RNA genome. To investigate novel PB2 antiviral target sites, this work identified evolutionary conserved regions across the PB2 protein sequence amongst all sub-types and hosts, as well as ligand binding hot spots which overlap with highly conserved areas. Fifteen binding sites were predicted in different PB2 domains; some of which reside in areas of unknown function. Virtual screening of ~50,000 drug-like compounds showed binding affinities of up to 10.3 kcal/mol. The highest affinity molecules were found to interact with conserved residues including Gln138, Gly222, Ile529, Asn540 and Thr530. A library containing 1738 FDA approved drugs were screened additionally and revealed Paliperidone as a top hit with a binding affinity of -10 kcal/mol. Predicted ligands are ideal leads for new antivirals as they were targeted to evolutionary conserved binding sites.


This document is the Accepted Manuscript version of the following article: Hershna Patel and Andreas Kukol, 'Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors', Virology, Vol. 509, pp. 112-120, June 2017. The version of record is available online at doi: © 2017 Published by Elsevier Inc.

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