In silico screening and identification of lead molecules with anti-hepatitis B activity

Abstract

Hepatitis B is an infectious liver disease which causes high morbidity and mortality worldwide. The present treatment of chronic hepatitis B (CHB) infection concentrates on clearing the HBV DNA and to prevent the development of complications. Currently seven drugs are available for the treatment of CHB: 5nucleo(S)tide analoque and 2 interferon based therapies. In order to find out safe and better drug, in the present investigation a total of 571 phytochemicals from three plants viz Elettaria cardamomum (L.) Maton, Curcuma longa and Zingiber Officinale were screened against three Hepatitis B Virus proteins such as HBx, HBc and polymerase (Poly) through docking using the tool AutoDock 4.2. For docking out of 571 phytochemicals derived from E. cardamomum (87), Z. officinale (273) and C. Longa (211), the structure of 558 compounds were downloaded form chemical databases and remaining 13 molecules structures were drawn using ChemSketech. The 3D structures of all phytochemicals structures were generated using the tool CORINA in .pdb format. The 3D structure of the target protein HBc was retrieved from Protein Data Bank (PDB ID:1QGT) and the structure of HBx and poly were modelled using the software MODELLER. The active site and residues of the target protein HBx and HBc was detected using PDB Sum and Poly was detected using CASTp. Docking was performed using the tool Auto Dock and the docked structures having binding energy <-5.0 kcal/mol were considered as the active/hit molecules. Top ranked five hit molecules with least binding energy obtained from each plant were further analysed based on other ctiteria such as hydrogen bond, other molecular interactive forces like hydrophobic interactions and drug likeness properties and selected the best lead molecules. The result showed that all three spices have inhibitory effect on the targets, HBX,HBc and poly. The best lead molecules selected against HBX was B-carotien (G bind <-11.40 kcal/mol) derived from Z.officinale and C. longa follewed by B-sitosterol (Gbind <-8.62 kcal/m0l) which was present in all the three plants. Similarlly, the best lead obtained against HBc was -ylangene (Gbind <-8.04 kcal/mol) from C. longa and Z.officinale and the compound 2-hydroxy methyl anthraquinone (-Gbind < -8.00 kcl/mol) present in E.cardamomum was also equallly competent as the best lead. Against polymerase vanilic acid (Gbind <-5.50 kcal/mol)was found as the best lead and it was present in all three plants. The compound p-hydroxy-benzoicacid obtained from Z. officinale and protocatechuic-acid from C.longa were also equally competent as the best lead. The results support the traditional knowledge and practice. However, based on the foregoing results in vitro and in vivo experiments are to be essential for further confirmation.