Discovery of Influenza Polymerase PA-PB1 Interaction Inhibitors Using an In Vitro Split-Luciferase Complementation-Based Assay.

ABSTRACT: The limited therapeutic options and increasing drug-resistance call for next-generation influenza antivirals. Due to the essential function in viral replication and high sequence conservation among influenza viruses, influenza polymerase PA-PB1 protein-protein interaction becomes an attractive drug target. Here, we developed an in vitro split luciferase complementation-based assay to speed up screening of PA-PB1 interaction inhibitors. By screening 10,000 compounds, we identified two PA-PB1 interaction inhibitors, R160792 and R151785, with potent and broad-spectrum antiviral activity against a panel of influenza A and B viruses, including amantadine-, oseltamivir-, or dual resistant strains. Further mechanistic study reveals that R151785 inhibits PA nuclear localization, reduces the

SUBMITTER: Zhang J 

PROVIDER: S-EPMC7028398 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature