Inhibition of enzymatic activities of Bothrops asper snake venom and docking analysis of compounds from plants used in Central America to treat snakebite envenoming

Snakebite envenoming is a serious medical problem in different areas of the world. In Latin America, the major prevalence is due to snakes of the family Viperidae, where rattlesnakes (Crotalus) are included. They produce hemotoxic venom which causes bleeding, tissue degradation and necrosis. Each venom has several enzymatic activities, producing different effects in the envenoming, doing its clinical effects difficult to study. Comparison between venom molecules is also difficult when different techniques are used, and therefore, their identification/characterization using the same methodology is necessary. In this work, a general biochemical characterization in snake venom of serine proteases (SVSP), phospholipases A2 (PLA2), metalloproteases (SVMP) and hyaluronidases (SVH) of Crotalus aquilus (Ca), Crotalus polystictus (Cp) and Crotalus molossus nigrescens (Cmn) was done. Differences in protein pattern, enzyme content and enzymatic activities were observed. All the venoms showed high PLA2 activity, high molecular weight SVSP, and a wide variety of SVMP and SVH forms. Ca and Cp showed the highest enzymatic activities of SVMP and SVSP trypsin-like and chymotrypsin-like, whereas Cmn showed the highest SVH and similar PLA2 activity with Ca. All the venoms showed peptides with similar molecular weight to crotamine-like myotoxins. No previous biochemical characterization of C. aquilus has been reported and there are no previous analyses that include these four protein families in these Crotalus venoms.

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ENZYMATIC ACTIVITIES AND OTHER CHARACTERISTICS OF CROTALUS VEGRANDIS SNAKE VENOM

Toxins ◽

10.1016/b978-0-08-022640-8.50025-1 ◽

1978 ◽

pp. 223-229 ◽

Cited By ~ 2

Author(s):

HÉCTOR R. SCANNONE ◽

OSWALDO GRILLO RODRÍGUEZ ◽

ABDEM R. LANCINI

Keyword(s):

Snake Venom ◽

Enzymatic Activities

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Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes

Biomedicines ◽

10.3390/biomedicines8060165 ◽

2020 ◽

Vol 8 (6) ◽

pp. 165 ◽

Cited By ~ 2

Author(s):

Chunfang Xie ◽

Laura-Oana Albulescu ◽

Kristina B. M. Still ◽

Julien Slagboom ◽

Yumei Zhao ◽

...

Keyword(s):

Phospholipase A2 ◽

Snake Venom ◽

Snake Venoms ◽

Venom Toxins ◽

Inhibitory Molecule ◽

Coagulation Assay ◽

Potential Clinical Utility ◽

Bothrops Asper ◽

Echis Carinatus ◽

Deinagkistrodon Acutus

Phospholipase A2 (PLA2) enzymes are important toxins found in many snake venoms, and they can exhibit a variety of toxic activities including causing hemolysis and/or anticoagulation. In this study, the inhibiting effects of the small molecule PLA2 inhibitor varespladib on snake venom PLA2s was investigated by nanofractionation analytics, which combined chromatography, mass spectrometry (MS), and bioassays. The venoms of the medically important snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus, Echis ocellatus, and Oxyuranus scutellatus were separated by liquid chromatography (LC) followed by nanofractionation and interrogation of the fractions by a coagulation assay and a PLA2 assay. Next, we assessed the ability of varespladib to inhibit the activity of enzymatic PLA2s and the coagulopathic toxicities induced by fractionated snake venom toxins, and identified these bioactive venom toxins and those inhibited by varespladib by using parallel recorded LC-MS data and proteomics analysis. We demonstrated here that varespladib was not only capable of inhibiting the PLA2 activities of hemotoxic snake venoms, but can also effectively neutralize the coagulopathic toxicities (most profoundly anticoagulation) induced by venom toxins. While varespladib effectively inhibited PLA2 toxins responsible for anticoagulant effects, we also found some evidence that this inhibitory molecule can partially abrogate procoagulant venom effects caused by different toxin families. These findings further emphasize the potential clinical utility of varespladib in mitigating the toxic effects of certain snakebites.

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