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
| Title | Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors. |
|---|---|
| Type | Journal article |
| Authors | Patel, H. and 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. |
| Keywords | influenza A, PB2, sequence conservation |
| Journal | Virology |
| Journal citation | 509, pp. 112-120 |
| ISSN | 0042-6822 |
| Year | 2017 |
| Publisher | Elsevier |
| 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 ID | 28628827 |
| Web address (URL) | https://www.sciencedirect.com/science/article/pii/S0042682217301861?via%3Dihub |
| Publication dates | |
| Published | 01 Sep 2017 |
| Funder | University of Hertfordshire |