Pharmacological Characterisation of Pseudocerastes and Eristicophis Viper Venoms Reveal Anticancer (Melanoma) Properties and a Potentially Novel Mode of Fibrinogenolysis
- Int J Mol Sci. 2021 Jun 27;22(13):6896. doi: 10.3390/ijms22136896.
- 1. Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
- 2. Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran 1983969411, Iran.
- 3. Institute of Inorganic and Analytical Chemistry, Justus Liebig University Giessen, 35392 Giessen, Germany.
- 4. Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.
- 5. H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan.
- 6. Department of Biology, Faculty of Science, Yasouj University, Yasouj 57914, Iran.
- 7. Division of Thrombosis & Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
- 8. Translational Venomics Group, Madrid Institute for Advanced Studies in Food, E28049 Madrid, Spain.
- 9. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
Venoms are a rich source of potential lead compounds for drug discovery, and descriptive studies of venom form the first phase of the biodiscovery process. In this study, we investigated the pharmacological potential of crude Pseudocerastes and Eristicophis Snake Venoms in haematological disorders and Cancer treatment. We assessed their antithrombotic potential using fibrinogen thromboelastography, fibrinogen gels with and without Protease Inhibitors, and colourimetric fibrinolysis assays. These assays indicated that the anticoagulant properties of the venoms are likely induced by the hydrolysis of Phospholipids and by selective fibrinogenolysis. Furthermore, while most fibrinogenolysis occurred by the direct activity of snake venom metalloproteases and serine proteases, modest evidence indicated that fibrinogenolytic activity may also be mediated by selective venom phospholipases and an inhibitory venom-derived serine Protease. We also found that the Pseudocerastes venoms significantly reduced the viability of human Melanoma (MM96L) cells by more than 80%, while it had almost no effect on the healthy neonatal foreskin fibroblasts (NFF) as determined by viability assays. The bioactive properties of these venoms suggest that they contain a number of toxins suitable for downstream pharmacological development as candidates for antithrombotic or Anticancer agents.