IDENTIFICATION OF LEAD COMPOUNDS WITH COBRA VENOM DETOXIFICATION ACTIVITY IN ANDROGRAPHIS PANICULATA (BURM. F.) NEES THROUGH IN SILICO METHOD

Objective: To validate the cobra venom detoxification activity in Andrographis paniculata and identification of lead molecules.Methods: The structures of phytochemicals were procured from databases or created by ChemSketch and CORINA. Of the14 cobra venom proteins selected as receptor molecules, the 3D structures of phospholipase A2 and cobrotoxin were retrieved from protein data bank and serine protease, L-amino acid oxidase and acetylcholinesterase were modelled. The structures of remaining nine proteins were retrieved from SWISSMODEL repository. The active sites of the receptor molecules were detected by Q-site Finder and Pocket Finder. Docking was carried out by AutoDock 4.2. To avoid error in lead identification, top ranked five hit molecules obtained in AutoDock were again docked by iGEMDOCK, FireDock and HEX server. The results were analyzed following Dempster-Shafer theory. The molecular property and biological activity of the lead molecules were predicted by molinspiration.Results: Docking results in AutoDock revealed that the plant having phytochemicals for detoxifying all venom proteins but only one potential hit molecule against each of the following proteins viz., cobramin A, cobramin B, long neurotoxin 1, long neurotoxin 2, long neurotoxin 3, long neurotoxin 4 and long neurotoxin 5 and several hit molecules (6-12) were obtained against phospholipase A2, cobrotoxin, cytotoxin 3, acetylcholinesterase, L-aminoacid oxidase, proteolase and serine protease. Therefore, in latter case lead molecules were identified through Dempster-Shafer theory. The theoretical prediction of drug likeliness and bioactivity of the molecules highlighted the plant as the best source of anti-cobra venom drug.Conclusion: The results substantiated its traditional use and further investigation on biological system is essential for evolving novel drug.Keywords: Andrographis paniculata, Cobra, Docking, Venom, Protein, Neurotoxin, Snake bit