Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors.

Patel, H. and Kukol, A 2017. Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors. Virology. 509, pp. 112-120. https://doi.org/10.1016/j.virol.2017.06.009

TitleEvolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors.
TypeJournal article
AuthorsPatel, H.
Kukol, A
Abstract

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.

Keywordsinfluenza A, PB2, sequence conservation
JournalVirology
Journal citation509, pp. 112-120
Year2017
PublisherElsevier
Accepted author manuscript
License
CC BY-NC-ND 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1016/j.virol.2017.06.009
PubMed ID28628827
Web address (URL)https://www.sciencedirect.com/science/article/pii/S0042682217301861?via%3Dihub
Publication dates
Published01 Sep 2017

Related outputs

Microbial Proteomics
Patel, H. and Whitehouse, D. 2019. Microbial Proteomics. in: Rapley, R. and Whitehouse, D. (ed.) Genomics and Clinical Diagnostics The Royal Society of Chemistry. pp. 103-139

Prediction of ligands to universally conserved binding sites of the influenza A virus nuclear export protein
Patel, H. and Kukol, A 2019. Prediction of ligands to universally conserved binding sites of the influenza A virus nuclear export protein. Virology. 537, pp. 97-103. https://doi.org/10.1016/j.virol.2019.08.013

Recent discoveries of influenza A drug target sites to combat virus replication
Patel, H. and Kukol, A 2016. Recent discoveries of influenza A drug target sites to combat virus replication. Biochemical Society Transactions. 44 (3), pp. 932-936. https://doi.org/10.1042/BST20160002

Evaluation of a novel virtual screening strategy using receptor decoy binding sites
Patel, H. and Kukol, A. 2016. Evaluation of a novel virtual screening strategy using receptor decoy binding sites. Journal of Negative Results in BioMedicine. 15, pp. 1-5. https://doi.org/10.1186/s12952-016-0058-8

Influenza A nucleoprotein binding sites for antivirals: current research and future potential
Patel, H. and Kukol, A 2014. Influenza A nucleoprotein binding sites for antivirals: current research and future potential. Future Virology. 9, pp. 625-627. https://doi.org/10.2217/fvl.14.45

Permalink - https://westminsterresearch.westminster.ac.uk/item/qz614/evolutionary-conservation-of-influenza-a-pb2-sequences-reveals-potential-target-sites-for-small-molecule-inhibitors


Share this
Tweet
Email

Usage statistics

5 total views
11 total downloads
0 views this month
2 downloads this month
These values are for the period from September 2nd 2018, when this repository was created

Export as