Development and validation of pharmacophore and QSAR models for influenza PB2 inhibitors

Abstract

The Swine influenza is a highly contagious respiratory disease caused by one of several swine influenza A viruses. The viral replication complex of H1N1, formed by three proteins PA, PB1 and PB2, plays a major role in host adaptation and subsequent infection. The conserved interaction sites of these three proteins have been suggested as potential drug targets and several inhibitors are designed for the purpose. We report a six featured 3D pharmacophore model based on 38 reported inhibitors of PB2. It was used for development of a statistically significant 3D QSAR model with R² = 0.70 (internal training set), R² = 0.67 (internal test set) and Q² (0.64). The predictive power of concerned pharmacophore model was validated with an external test set R² (0.54) and used for screening of filtered PubChem database to fetch some important molecules. Both pharmacophore and QSAR models gave detailed structural insights as well as highlighted important features which can help in the design of potential PB2 inhibitors in future.