Patel H, Kukol A.. Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors. Virology 2017;509:112-120.
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 -10.3kcal/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 was screened additionally and revealed Paliperidone as a top hit with a binding affinity of -10kcal/mol. Predicted ligands are ideal leads for new antivirals as they were targeted to evolutionary conserved binding sites.
See Also:
Latest articles in those days:
- [preprint] Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle 12 minute(s) ago
- Modelling the transmission dynamics of H9N2 avian influenza viruses in a live bird market 14 minute(s) ago
- CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age 3 days ago
- Surveillance for highly pathogenic avian influenza A (H5N1) in a raptor rehabilitation center-2022 3 days ago
- [preprint]Detection of hemagglutinin H5 influenza A virus sequence in municipal wastewater solids at wastewater treatment plants with increases in influenza A in spring, 2024 3 days ago
[Go Top] [Close Window]