Effect of aqueous root extract of Cynodon dactylon on the hemolytic activity of cardiotoxins from Indian cobra (Naja naja)

Snake venoms are a complex blend of enzymes and proteins/peptides depicting diverse pharmacological properties.Snakebite envenomation causes considerable morbidity and mortality worldwide, especially in rural regions. Atpresent, the only available remedy for snakebite is polyvalent antivenoms and the antivenoms are shown to developadverse effects such as anaphylaxis and pyrogen reactions. In the present study, we have examined antihemolyticactivity of aqueous root extract of Cynodon dactylon against cardiotoxins belonging to three-finger toxin family ofthe Indian cobra crude venom. The aqueous root extract of the Cynodon dactylon was found to have remarkableantihemolytic potential against the crude venom as probed by in vitro assay. In this background, the phytochemicalspresent in the Cynodon dactylon extract were delineated using mass spectrometry data obtained for the extract andthe compounds were then subjected to high-throughput virtual screening. A comprehensive analysis of the moleculardocking data paved a way to identify a few lead antihemolytic chemical compounds from the plant extract. Scopes toexplore structural determinants for the interaction between the chemical molecules and target protein toxins at highresolutions have also been discussed.

Crucial Residues Modulating Interface of hBcl-B - hBaxBH3 Heterodimer as Probed by Computational Methods

ABSTRACT Cancerous cells develop resistance to cell death by over expression of anti-apoptotic proteins, which are specific to interact with pro-apoptotic and BH3-only proteins of Bcl-2 family. Delineating crucial residues mediating the heterodimer complexes (anti-apoptotic proteins - pro-apoptotic/BH3-only proteins) is indispensable to develop specific antagonists to anti-apoptotic proteins. In these backgrounds, we have herein reported crucial residues of hBaxBH3 and hBcl-B (an anti-apoptotic protein specifically interacts with human Bax but does not interact with human Bak) for hetero dimerization of the polypeptides and as well validated the structural determinants of the polypeptides through variety of virtual 'alanine mutants' and 'switch mutants' by using an array of computational methods. Residues such as D53, S60, E61, K64, E69 and D71 of hBaxBH3 and R45, H50, F53, F54, Y57, M71, S74, V75, R86, V88, T89, F93 and F159 of hBcl-B were found to be crucial residues of the polypeptides for intermolecular interaction leading hetero dimerization. Moreover, 'pharmacophoric residues' for the hBaxBH3 and hBcl-B have also been figured out and rationalized.