Unraveling the Proteome Composition and Immuno-profiling of Western India Russell's Viper Venom for In-Depth Understanding of Its Pharmacological Properties, Clinical Manifestations, and Effective Antivenom Treatment

J Proteome Res. 2017 Feb 3;16(2):583-598. doi: 10.1021/acs.jproteome.6b00693. Epub 2016 Dec 12.

Abstract

The proteome composition of western India (WI) Russell's viper venom (RVV) was correlated with pharmacological properties and pathological manifestations of RV envenomation. Proteins in the 5-19 and 100-110 kDa mass ranges were the most predominate (∼35.1%) and least abundant (∼3.4%) components, respectively, of WI RVV. Non-reduced SDS-PAGE indicated the occurrence of multiple subunits, non-covalent oligomers, self-aggregation, and/or interactions among the RVV proteins. A total of 55 proteins belonging to 13 distinct snake venom families were unambiguously identified by ESI-LC-MS/MS analysis. Phospholipase A2 (32.5%) and Kunitz-type serine protease inhibitors (12.5%) represented the most abundant enzymatic and non-enzymatic proteins, respectively. However, ATPase, ADPase, and hyaluronidase, detected by enzyme assays, were not identified by proteomic analysis owing to limitations in protein database deposition. Several biochemical and pharmacological properties of WI RVV were also investigated. Neurological symptoms exhibited by some RV-bite patients in WI may be correlated to the presence of neurotoxic phospholipase A2 enzymes and Kunitz-type serine protease inhibitor complex in this venom. Monovalent antivenom was found to be better than polyvalent antivenom in immuno-recognition and neutralization of the tested pharmacological properties and enzyme activities of WI RVV; nevertheless, both antivenoms demonstrated poor cross-reactivity and neutralization of pharmacological activities shown by low-molecular-mass proteins (<18 kDa) of this venom.

Keywords: ESI-LC-MS/MS; anti-coagulant; neurotoxicity; pro-coagulant; venom proteome; venom−antivenom cross-reactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antivenins / isolation & purification
  • Antivenins / pharmacology*
  • Chemical Fractionation
  • Daboia / physiology
  • Electrophoresis, Polyacrylamide Gel
  • Gene Ontology
  • Horses
  • Humans
  • Immune Sera / chemistry
  • Molecular Sequence Annotation
  • Molecular Weight
  • Phospholipases A2 / chemistry
  • Phospholipases A2 / isolation & purification*
  • Protein Aggregates
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / chemistry
  • Protein Subunits / isolation & purification*
  • Proteome / antagonists & inhibitors
  • Proteome / chemistry
  • Proteome / isolation & purification*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / isolation & purification*
  • Spectrometry, Mass, Electrospray Ionization
  • Viper Venoms / antagonists & inhibitors
  • Viper Venoms / chemistry*

Substances

  • Antivenins
  • Immune Sera
  • Protein Aggregates
  • Protein Subunits
  • Proteome
  • Serine Proteinase Inhibitors
  • Viper Venoms
  • Phospholipases A2