Quantum modelling analysis of some potent indole derivatives on NS5B polymerase inhibitors

Abstract

Viral hepatitis C infection is one of the main causes of the hepatitis after blood transfusion, hepatitis C virus (HCV) infection is a global health threat. The Non-structural viral protein (NS5B) is one of the best-studied polymerase which emerged as an attractive target for the development of novel therapeutics against hepatitis C virus. Quantitative structure-activity relationship studies (QSAR) was carried out on a series of indole derivatives as anti-hepatitis C inhibitors. Density Functional Theory (DFT) quantum chemical calculation method was used to find the optimized geometry of the indole inhibitors. Five types of molecular descriptors were used to derive a quantitative relation between indole activity and structural properties. The relevant molecular descriptors were selected by Genetic Function Algorithm (GFA). The best model (model 1) was validated and found to be statistically significant with squared correlation coefficient of R² of 0.969, R²adj value 0.917, and Q² LOO 0.612 and the external validation was found to be R² pred. = 0.815. The proposed model has good stability, robustness, and predictability on verifying with internal and external validation. The physicochemical parameters are to be considered when improving the inhibitory activities of the indole derivatives against an enzyme that causes HCV (NS5B polymerase).