Objective: In folk and TCM clinical medicine, Chinese herbal medicine is used to treat snakebite and has good curative effect, but its active ingredients and mechanism are still unclear. In this study, virtual screening and mechanism analysis of effective components from 6 Chinese herbs to inhibit phospholipase A2 of Deinagkistrodonacutus (dPLA2) venom were conducted. Methods: With advanced computing software AutoDock, Pymol and GROMACS, the molecules selected from the Chinese herbal Medicine Chemical Composition databas6e (TCMSP) were docked with the dPLA2 from the protein database (PDB). Further molecular dynamics simulation was used to evaluate the molecular binding stability. Results: Four potential dPLA2-inhibiting molecules were screened: lobelanidine, lobeline, norlobelanine and pratensein, by analyzing the spatial structure, binding energy and binding interaction of small molecular-dPLA2 complexes, as well as the RMSD and RMSF of molecular dynamics simulation. Conclusion: To our knowledge, this is the first report of lobeline has an inhibitory effect on dPLA2, and lobelanidine, as a precursor of lobeline, has a stronger inhibitory effect. According to the docking results, it is speculated that the mechanism of action of the four molecules is to form stable interactions with calcium ions and amino acid residues on the calcium ion binding ring in dPLA2. Moreover, these small molecules compete with phosphatidylcholine (the natural substrate of dPLA2) to bind dPLA2 and have a higher affinity than phosphatidylcholine, resulting in inhibition of dPLA2 activity.
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