Bioefficacy, chromatographic profiling and drug-likeness analysis of flavonoids and terpenoids as potential inhibitors of H1N1 influenza viral proteins

Abstract

Considering medicinal plants, natural products present in these plants are the best sources of medications for combating viral infection. The possible drug target against viral H1N1 influenza proteins lead to identification of selected secondary metabolites from potential plants Tinospora cordifolia, Ocimum sanctum, and Piper nigrum. On analysis of in vitro cell based antiviral activity of the selected plant extracts, an indication for a possible lead compound against neuraminidase activity was evident. Potent ligands were selected using drug docking and ADMET analysis, and the screened lead metabolites were ultimately identified as terpenoid (Columbin) and, flavonoid (Cubebin, and Apigenin). Among the selected ligands, the drug binding activity of Cubebin with all the 6 proteins of H1N1 influenza type A virus, HA (4r8w), NA (4qn7), M2 (3lbw), PA (4wsb), PB1 (2znl) and PB2 (3wil), was pronounced. In addition, physicochemical and pharmacokinetic parameters linked to absorption, distribution, metabolism, excretion and toxicity (ADMET) have been evaluated and corroborate with our in vitro results. Molecular dynamics modelling indicated Cubebin can be a potential phytochemical in a drug discovery pipeline for the development of neuraminidase inhibitors. Further studies can provide a possibility for an alternative therapy against Influenza viruses.