In Silico Prediction of High Potential Jararhagin Inhibitor: Comparison of Batimastat, EDTA and Hydroxytyrosol

Abstract

: One example of a group P-III SVMP is jararhagin which originates from a Bothrops jararaca . This study was conducted to compare the possibility of inhibitors that have the highest effectiveness and exact time of each compound to inhibit hemorragic effect of SVMP. Inhibition of hemorrhagic activity can be done with several types of compounds that have been known to be inhibitors for SVMP especially jararhagin (PDB ID: 1C9G) to bind with integrin  2  1 (PDB ID: 1AOX). There are batimastat (PubChem ID: 5362422) as one of peptidomimetic compounds, EDTA (PubChem ID: 6049) as one of zinc chelating agents, and plant compounds such as hydroxytyrosol (PubChem ID: 82755). The batimastat inhibitory properties from value of binding energy, found that these inhibitor were more easily bound to jararhagin (-289.0 kcal/mol) compared to integrin  2  1 (-277.1 kcal/mol). That inhibitor also more effectively inhibited by bounding to jararhagin spread in blood vessels after snakebite because of it’s position and more positive binding energy (-784.1 kcal/mol). However, unfavorable bonds are formed in the interaction between batimastat inhibitors, jararhagin and integrin  2  1 . In inhibitor EDTA interaction, it was found that this compound also more easily bound to jararhagin (-227.23 kcal/mol), but this inhibitor are more effectively inhibited by bounding to integrin  2  1 because of it’s position and more positive binding energy (-721.57 kcal/mol). In other side it also has unfavorable bonds. While the interaction of hydroxytyrosol shows that inhibitor are easier to interact with jararhagin and more effectively acts as a jararhagin inhibitor by being consumed after the body is exposed to jararhagin (-781.33 kcal/mol) without showing an unfavorable bond. We can conclude that the natural inhibitors formed in hydroxytyrosol from olive oil are more stable and have highest possibility in preventing hemorrhagic symptoms