Pharmacological Characterisation of <i>Pseudocerastes</i> and <i>Eristicophis</i> Viper Venoms Reveal Anticancer (Melanoma) Properties and a Potentially Novel Mode of Fibrinogenolysis

• Main Authors: Bianca op den Brouw, Parviz Ghezellou, Nicholas R. Casewell, Syed Abid Ali, Behzad Fathinia, Bryan G. Fry, Mettine H.A. Bos, Maria P. Ikonomopoulou
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: International Journal of Molecular Sciences
• Subjects: venom; <i>Pseudocerastes</i>; <i>Eristicophis</i>; biodiscovery; melanoma; cancer
• Online Access: https://www.mdpi.com/1422-0067/22/13/6896
• ISSN: 1661-6596; 1422-0067

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 <i>Pseudocerastes</i> and <i>Eristicophis</i> 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 <i>Pseudocerastes</i> 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.