Hepatitis C virus (HCV) is a serious medical issue, which results in several severe clinical conditions varying from acute viral hepatitis to chronic liver disease and eventually leading to liver cirrhosis. It is one of the major factors responsible for liver cancer and approximately around 3% of the world’s population, are chronically affected with HCV [1]. Although there is no vaccine available to completely treat HCV caused infection. However, the current clinical method of curing includes a combination of peg-IFN (pegylated interferon) with the nucleoside analog with RBV (ribavirin) [2]. Literature [3] has reported that the activity of the virally encoded HCV NS5B polymerase is essential for HCV replication making it an attractive target for the development of novel anti-HCV drugs. In particular, 5,6-dihydro-1H-pyridin-2-one derivatives [4] have been reported to be potent inhibitors of NS5B polymerase.
In this study, we explored the electronic properties and inhibition activity of three compounds who were reported to be active against NS5B polymerase enzyme, using quantum chemical and molecular docking calculations. Quantum chemical methods have already been proven to be crucial in determining the molecular structure as well as elucidating the electronic properties and reactivity of a variety of biologically significant molecules [5–9]. Although, there are several quantum chemical methods available, but, density functional theory (DFT) based methods have gained much popularity due to their better compromise between computational cost and offered accuracy. DFT methods generally provide the electronic energy and related parameters as a function of electron density, which is itself a function of position coordinates. In the current scenario, available DFT methods are capable enough to reproduce experimental data such as geometrical structural parameters viz., bond length, bond angle, dihedral, etc. [10, 11] and spectral parameters viz., FT-IR, NMR, UV-vis, etc. and to later provide accurate predictions of the same in case of absence of the experimental data. Considering these points, we present DFT calculations on chemical properties of three NS5B polymerase inhibitors belonging to 5,6-dihydro-1H-pyridin-2-one series of compounds, followed by docking studies for potent applications of the mentioned compounds as HCV-NS5B Polymerase inhibiters.