Next Article in Journal
Mitochondrial Dysfunction and DNA Damage in the Context of Pathogenesis of Atherosclerosis
Next Article in Special Issue
It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula
Previous Article in Journal
Air Contamination in Different Departments of a Tertiary Hospital. Assessment of Microbial Load and of Antimicrobial Susceptibility
Previous Article in Special Issue
Characterization of Synthetic Tf2 as a NaV1.3 Selective Pharmacological Probe
Open AccessArticle

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

1
Amsterdam Institute of Molecular and Life Sciences, Division of BioAnalytical Chemistry, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
2
Centre for Analytical Sciences Amsterdam (CASA), 1098 XH Amsterdam, The Netherlands
3
Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
4
Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
5
Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University, Huangpu Avenue West 601, Guangzhou 510632, China
6
Naturalis Biodiversity Center, Darwinweg 2, 2333 CR Leiden, The Netherlands
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(6), 165; https://doi.org/10.3390/biomedicines8060165
Received: 10 May 2020 / Revised: 4 June 2020 / Accepted: 11 June 2020 / Published: 17 June 2020
(This article belongs to the Special Issue Animal Venoms–Curse or Cure?)
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. View Full-Text
Keywords: varespladib; nanofractionation; PLA2 activity; coagulopathic toxicity; neutralization varespladib; nanofractionation; PLA2 activity; coagulopathic toxicity; neutralization
Show Figures

Figure 1

MDPI and ACS Style

Xie, C.; Albulescu, L.-O.; Still, K.B.M.; Slagboom, J.; Zhao, Y.; Jiang, Z.; Somsen, G.W.; Vonk, F.J.; Casewell, N.R.; Kool, J. Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes. Biomedicines 2020, 8, 165.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop