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Inhibitory effects of ascorbic acid toward snake venom metalloproteinase (SVMP) from Indian Echis carinatus venom: Insights from molecular modeling and binding studies
Author(s) -
Choudhury Manisha,
Senthilvadivel Vajravijayan,
Velmurugan Devadasan
Publication year - 2018
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22224
Subject(s) - ascorbic acid , venom , envenomation , antivenom , snake venom , biochemistry , viper , metalloproteinase , chemistry , pharmacology , viperidae , disintegrin , matrix metalloproteinase , biology , food science
Abstract Classical antivenom therapy is unable to shield complications of viper bite and has limitations such as anaphylaxis and serum sickness. Snake venom metalloproteinases are responsible for local tissue damage and hemorrhage at the bitten site in viper envenomation, and this has led to a persistent search for metalloproteinase inhibitors. Here, we report the inhibitory effects of ascorbic acid against metalloproteinase from Echis carinatus venom both in‐silico and in‐vitro. Ascorbic acid effectively inhibited the proteolytic activity of E. carinatus venom in a dose‐dependent manner. Interaction studies of ascorbic acid with purified ecarin using isothermal titration calorimetry showed favorable binding energy and energetics. The molecular docking of ascorbic acid with ecarin revealed important interactions with residues at the active site pocket of ecarin. It was observed that the ligand behaves as a chelating inhibitor. Thus, the backbone structural scaffold of ascorbic acid can find potential use as building blocks in designing drug‐like molecules for viper bite management.