title: Large-scale analysis of influenza A virus nucleoprotein sequence conservation reveals potential drug-target sites.
abstract: The nucleoprotein (NP) of the influenza A virus encapsidates the viral RNA and participates in the infectious life cycle of the virus. The aims of this study were to find the degree of conservation of NP among all virus subtypes and hosts and to identify conserved binding sites, which may be utilised as potential drug target sites. The analysis of conservation based on 4430 amino acid sequences identified high conservation in known functional regions as well as novel highly conserved sites. Highly variable clusters identified on the surface of NP may be associated with adaptation to different hosts and avoidance of the host immune defence. Ligand binding potential overlapping with high conservation was found in the tail-loop binding site and near the putative RNA binding region. The results provide the basis for developing antivirals that may be universally effective and have a reduced potential to induce resistance through mutations.
authors.affiliation: School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK. Electronic address: a.kukol@herts.ac.uk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kukol
authors.affiliation: School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK.
authors.forename: David John
authors.initials: DJ
authors.lastname: Hughes
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology; D001665:Binding Sites; D017124:Conserved Sequence; D055808:Drug Discovery / Q000379:methods; D009980:Influenza A virus / Q000235:genetics*; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins / Q000235:genetics*; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins
keywords: Binding site; Drug target; Evolution; Protein structure; Sequence conservation