Abstract
Snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) are among the most abundant enzymes in many snake venoms, particularly among viperids. These proteinases are responsible for some of the clinical manifestations classically seen in viperid envenomings, including hemorrhage, necrosis, and coagulopathies. The objective of this study was to investigate the enzymatic activities of these proteins using a high-throughput peptide library to screen for the proteinase targets of the venoms of five viperid (Echis carinatus, Bothrops asper, Daboia russelii, Bitis arietans, Bitis gabonica) and one elapid (Naja nigricollis) species of high medical importance. The proteinase activities of these venoms were each tested against 360 peptide substrates, yielding 2160 activity profiles. A nonlinear regression model that accurately described the observed enzymatic activities was fitted to the experimental data, allowing for the comparison of cleavage rates across species. In this study, previously unknown protein targets of snake venom proteinases were identified, potentially implicating novel human and animal proteins that may be involved in the pathophysiology of viper envenomings. The functional relevance of these targets was further evaluated and discussed. These new findings may contribute to our understanding of the clinical manifestations and underlying biochemical mechanisms of snakebite envenoming by viperid species.
Highlights
Snake venoms are highly complex mixtures of proteins and peptides, comprising enzymes, non-enzymatic proteins and polypeptides from a wide range of families, and other bioactive components [1,2]
Based on the modeling parameter estimation of activity, and the number of cleaved substrates of these snake venoms in the substrate set as a whole, the highest activity was observed for the venoms of E. carinatus, B. arietans, and B. asper
The results of the high-throughput peptide screening analysis provide a general overview of the magnitude of proteinase activity for each snake venom, and provide insights into relevant targets for the enzymes involved in the pathophysiology of snakebite envenomings
Summary
Snake venoms are highly complex mixtures of proteins and peptides, comprising enzymes, non-enzymatic proteins and polypeptides from a wide range of families, and other bioactive components [1,2]. Proteinases are prevalent enzymes in the venoms of snakes in the Viperidae family [3,4,5,6], and are often the main drivers of toxicity for viperid venoms. These enzymes are known to affect a large number of physiological pathways and response cascades, assisting in immobilization and death. Toxins 2019, 11, 170 other proteins may become activated or deactivated. This may modulate different physiological processes involved in homeostasis [8]
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