In silico evaluation of anti-cobra venom activity in selected fruit crops

Abstract

In the present investigation, a total of 522 phytochemicals from five plant species viz. P. granatum, S. cumini, M. indica, T. indica and P. emblica were selected as ligand molecules against 14 cobra venom toxic proteins such as PLA 2, CBT, LN 1, LN 2, LN 3, LN 4, LN 5, CA, CB, CYT 3, PRT, ACE, LAAO and SP and were docked using the tool AutoDock 4.2. The 3D structures of the target proteins were procured from databases or modeled structures procured from earlier authors and 519 phytochemicals procured from databases and remaining three molecules structures were created using the tool ChemSketch and its 3D structures were created in CORNIA. The docked structures with least binding energy, hydrogen bond and having hydrophobic interaction with critical residue were selected as the best lead molecule. The results showed that Mangifera indica can inhibit all the 14 cobra venom proteins. P. granatum, P. emblica and T. indica have no inhibitory compounds against CA and in case of S. cumini and T. indica, they don’t have inhibitory compound against LN 2. In order to find out best lead molecule from these 522 phytomolecules against each venom protein without any error, top ranked five lead molecules were again docked using the tools Hex Server, PatchDock and iGEMDOCK and the results were subjected to DST analysis and selected the best lead molecules against nine proteins from M. indicia, two from P. granatum, two from P. emblica and one from T. indica. The best lead from M. indicia were 7-epi-a-selinene (-6.06 kcal/mol) on LN 1 and LN 3, mangiferolic acid on LN 4, ambolic acid on LN 5, 1-epi-cubenol on CA, isomangiferolic acid on CYT 3, mangiferonic acid on PRT and SP and mangiferolic acid on LAAO. The two best lead obtained from P. granatum were gamma sitosterol on PLA 2 and beta sitosterol on ACE. Similarly from P. emblica were betulonic acid on LN 2 and phyllantidine on CB and the only one best lead obtained from T. indica was procyanidin dimer on CBT. It was also noted that many lead molecules have multi- protein inhibitory activity. The overall results substantiated the traditional use of these plants as antidote to cobra venom. In vitro and in vivo experiments are to be essential for further confirmation.