Plant-derived antiviral drugs as novel hepatitis B virus inhibitors: Cell culture and molecular docking study

Parvez, Mohammad K.; Tabish Rehman, Md.; Alam, Perwez; Al-Dosari, Mohammed S.; Alqasoumi, Saleh I.; Alajmi, Mohammed F.

The modeled HBV Pol was used as receptor for screening the binding modes of antiviral natural compounds, including lamivudine ( Fig. 1) in Autodock Vina and PyRx virtual screening tools (Trott and Olson, 2010; Dallakyan and Olson, 2015) . All compounds were energy minimized using Universal Force Field (UFF). The compounds showing DG ! À6.0 kcal/mol were re-docked to HBV Pol to evaluate their detailed binding mechanisms using Autodock 4.2 as described elsewhere (Morris et al., 2009; Al-Yousef et al., 2017) . For molecular docking, target protein and ligands were prepared as described elsewhere (Rehman et al., 2014; Rabbani et al., 2017) . Briefly, the target model protein HBV Pol was prepared by removing any heterogeneous compounds and water molecules. Polar hydrogen atoms and Kollman charges were added to the protein using Autodock tool (ADT). Affinity grid maps were generated in such a way as to cover the complete active sites of the protein. Molecular docking was performed using Lamarkian Genetic Algorithm (LGA) to calculate the possible conformations of the ligands that bind to the target protein. Here, the ligand was set free to search and bind at the active site of the protein in the most favorable or minimum energy conformation. Initial positions and orientations of the ligands were set randomly while the torsions were set to a maximum of 6. Each run of the docking was performed to calculate 2,500,000 energy evaluations. The population size, translational step, quaternion and torsion steps were set to 150, 0.2 and 5 respectively. On the basis of binding energy (DG), best docked structures were saved and analyzed for receptor-ligand interactions using Discovery Studio 4.0 (Accelrys Software Inc., 2012). The binding constant (K b ) for protein-ligand interaction was calculated using the following relation (Rehman et al., 2016) : DG ¼ ÀRTlnK b (R = gas constant, 1.987 cal/mol/K; T = temperature, 298 K). Fig. 1 . Structures of the studied antiviral compounds (lamivudine, quercetin, rutin, hesperidin, lupeol, azadirachtin, b-sitosterol, psoralen, embelin, menisdaurin, and baccatin III). Source: https://pubchem.ncbi.nlm.nih.gov/.