Polymerase Acidic Protein–Basic Protein 1 (PA–PB1) Protein–Protein Interaction as a Target for Next-Generation Anti-influenza Therapeutics

摘要: The limited therapeutic options against the influenza virus (flu) and increasing challenges in drug resistance make search for next-generation agents imperative. In this context, heterotrimeric viral PA/PB1/PB2 RNA-dependent RNA polymerase is an attractive target a challenging but strategic protein-protein interaction (PPI) inhibition approach. Since 2012, of PA-PB1 subunit interface has become active field research following publication crystal structures. Perspective, we briefly discuss validity flu as its through PPI strategy, including comprehensive analysis available An overview all reported complex formation inhibitors provided, approaches used identification inhibitors, hit-to-lead studies, emerged structure-activity relationship are described. addition to highlighting strengths weaknesses heterodimerization analyze their hypothesized binding modes alignment with pharmacophore model that have developed.