Molecular docking studies of phytochemicals from Phyllanthus niruri against Hepatitis B DNA Polymerase

Abstract

Hepatitis B virus (HBV) infection is the leading cause for liver disorders and can lead to hepatocellular carcinoma, cirrhosis and liver damage which in turn can cause death of patients. HBV DNA Polymerase is essential for HBV replication in the host and hence is used as one of the most potent pharmacological target for the inhibition of HBV. Chronic hepatitis B is currently treated with nucleotide analogues that suppress viral reverse transcriptase activity and most of them are reported to have viral resistance. Therefore, it is of interest to model HBV DNA polymerase to dock known phytochemicals. The present study focuses on homology modeling and molecular docking analysis of phytocompounds from the traditional antidote Phyllanthus niruri and other nucleoside analogues against HBV DNA Polymerase using the software Discovery studio 4.0. 3D structure of HBV DNA Polymerase was predicted based on previously reported alignment. Docking studies revealed that a few phytochemicals from Phyllanthus niruri had good interactions with HBV DNA Polymerase. These compounds had acceptable binding properties for further in vitro validation. Thus the study puts forth experimental validation for traditional antidote and these phytocompounds could be further promoted as potential lead molecule.

Keywords: Hepatitis B; Homology modeling; Molecular Docking; Phyllanthus niruri; Phytochemicals.

Figure 1

Homology modeling and validation of model: A) Validation using Ramachandran plot. Summary of the plot is as follows: Residues in favored regions- 257 (84.3%), Residues in additionally allowed regions- 39 (12.5%), Residues in generously allowed regions-6 (2.0%) and Residues in disallowed regions- 3 (1.0%); B) PROSA Z score for model. The Z score for the model was -3.39; C) Homology model of HBV-DP created using Pymol software.

Figure 2

Residues involved in the binding cavity of HBV-DP. The figure shows the residues in the active site of the target protein (HBV-DP). The figure was made in Pymol software by implementing ‘surface’ and ‘stick’ representations and was colored accordingly

Figure 3

Ethyl brevifolincarboxylate docked to the active site residues in the protein. The figure shows the hydrogen bond distances between Ethyl brevifolincarboxylate and the active site residues (LYS32, ARG41, ALA87, PHE88 and ASP205).The distances are within 2.5Å distance which indicates strong binding.