Inhibition of Influenza Virus Polymerase by Interfering with Its Protein-Protein Interactions.

摘要: Influenza (flu) virus is a serious threat to global health with the potential generate devastating pandemics. The availability of broad spectrum antiviral drugs an unequaled weapon during pandemic events, especially when vaccine still not available. One most promising targets for development new antiflu therapeutics viral RNA-dependent RNA polymerase (RdRP). assembly flu RdRP heterotrimeric complex from individual acidic protein (PA), basic 1 (PB1), and 2 (PB2) subunits prerequisite functions, such as mRNA synthesis genome replication. In this Review, we report known protein-protein interactions (PPIs) occurring by that could be disrupted small molecules analyze their benefits drawbacks drug targets. An overview able interfere functions exploiting PPI inhibition approach described. particular, update on recent inhibitors targeting well-consolidated PA-PB1 subunit heterodimerization mainly reported, together pioneer other virus-virus or virus-host involving subunits. As demonstrated interaction discussed herein, disrupters clearly represents valid means identify compounds endowed action reduced propensity develop resistance, which are main issues drugs.