Structure-Based Virtual Screening for Potential Inhibitors of Influenza A Virus RNA Polymerase PA Subunit

The amino terminus of RNA polymerase A (PA-N) of influenza virus is an important target for the design of new antiviral agents. In this study, molecular docking was used to screen for compounds that specifically target the deep cleft at the endonuclease active site in N-terminus of the RNA polymerase. Four potential compounds (NCI100226, NCI122653, NCI625583, and NCI403587) with high binding affinity for the active site were identified. Structural analysis of the binding conformation of each of these compound-PA-N complexes revealed that hydrophobic interaction and manganese ion chelation comprised the main interaction between the compounds and enzyme. The binding configuration stability and the number of hydrogen and ionic bonds were investigated by molecular dynamic simulations. The results indicated that NCI403587 could be a promising PA-N inhibitor, and may represent a potential new agent for the treatment of influenza.