Identification of structural requirements and prediction of inhibitory activity of natural flavonoids against Zika virus through molecular docking and Monte Carlo based QSAR Simulation

Abstract

There has been growing interest in the research of flavonoids due to their potential antiviral activities. Recently, some natural flavonoids have shown potential inhibitory activity against zika virus NS3–NS2B protease. In order to accelerate the drug discovery efforts using flavonoids, a Monte Carlo simulation-based QSAR method has been applied to find out the structural requirements for the inhibitory activity. The best QSAR model was obtained using SMILES descriptors and HSG descriptors with 1EC connectivity with the following statistical parameters: R2 = 0.9569 and Q2 = 0.9050 for the test set. The best model was further utilised for the prediction of inhibitory activity of some other natural flavonoids. Four flavonoids (amentoflavone, fisetin, isorhamnetin and theaflavin-3-gallate) have shown higher predicted inhibitory activity and further validated by performing docking analysis. This study may help in understanding and performing natural flavonoids-based drug discovery against zika virus.