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.

HBV Pol has been the most desired target protein to develop potential anti-HBV nucleot(s)ide drugs despite emergence of drug-resistant mutations in the Pol 'YMDD' motif (Lok et al., 2007; Locarnini et al., 2008) . Since the crystal structure of HBV Pol was not available, we used homology modeling to predict its three-dimensional structure. It has been reported that the amino acid residues from 347 to 698 determine the reverse transcriptase activity of HBV Pol. We therefore, used the above sequence as query to search protein database for the identification of the most suitable template. Based on the primary sequence alignment (Fig. 6A) , we used HIV-1 RT (PDB Id: 1RTD) as a template for HBV Pol homology modeling because the two viral proteins demonstrated highly conserved residues important for enzymatic activities. The homology model of HBV Pol was generated using the Swiss model server (Fig. 6B) , and validated by Ramachandran plot. The Ramachandran plot showed 75.2% of the residues occupying the favored region, while 19.0% and 3.9% residues occupied the allowed and generously allowed region, respectively. Only, 2.0% of the residues were located in the disallowed outlier region (Fig. 5C ). Overall the Ramachandran plot suggested that the generated model of HBV Pol was of reasonably good quality and therefore, used for molecular docking.