Characterisations and Molecular Docking of Cathepsin B Cysteine Proteinase a novel drug target for Parasitic Nematode Trichinella spiralis.

Abstract

Abstract Trichinella spiralis is a nematode parasite, the common cause of human disease Trichinellosis, the infection occurs after the consumption of raw or undercooked pork meat. In many parasitic helminths Cysteine proteases are the principal source of amino acids. In Trichinella spiralis, cathepsin B cysteine proteases may contribute to the parasite penetration into the host’s gut wall, feeding, degradation of haemoglobin etc. The aim of this study is to characterise and inhibit the synthesis of cathepsin B cysteine proteases by using natural product as inhibitors of protein to control the population of nematode parasite in human host. The EXPASY server ProtParam performed the cysteine protease cathepsin B physicochemical analysis. In secondary structure analysis amino acid composition of cathepsin B protein were predicted by PredictProtein. Based on ADMET properties analysis and binding affinities of all the studied phytochemicals originated molecules Panduratin A, Nicolaioidesin C, Guttiferone A, Garciniaphenone, shows drugability. The AutoDock automated docking tools were used for molecular docking analysis and predicting the optimal protein-ligand interactions between the cathepsin B and Panduratin A, Nicolaioidesin C, Guttiferone A, Garciniaphenone. Insilico analysis of Cathepsin B (329 amino acids) shows that it is quite stable protein with Aliphatic index 65.84 and composed of helix is 15.81%, strand 17.02% and other part is 67.17%. The molecular docking analysis results revealed that amongst the studies ligands Panduratin A and Nicolaioidesin C, shows the similar affinity towards protein i.e. (-7.5 Kcl/mol) with formation of 2 and 3 hydrogen bond interactions respectively, While Guttiferone A (-7.4 Kcl/mol) 4 hydrogen bond interactions and Garciniaphenone (-7.2 Kcl/mol) 3 hydrogen bond interactions. The small molecule as inhibitors and understanding their utility as vaccine candidate against nematodes is recent active area of research. These results indicates that the cathepsin B which is the key contributors to the digestion of host proteins of the Trichinella spiralis parasite may be a good candidate to design the synthetic drug against the nematode infections.