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J Biochem Mol Toxicol ; 32(12): e22224, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30276921

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.


Subject(s)
Ascorbic Acid/pharmacology , Metalloproteases/antagonists & inhibitors , Protease Inhibitors/pharmacology , Viper Venoms/enzymology , Viperidae/metabolism , Animals , Ascorbic Acid/chemistry , Calorimetry , Dose-Response Relationship, Drug , Endopeptidases/pharmacology , Metalloproteases/chemistry , Metalloproteases/metabolism , Models, Molecular , Protein Binding , Proteolysis/drug effects , Viper Venoms/toxicity
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