Scorpion Venom–Toxins that Aid in Drug Development: A Review
Abstract
Scorpion venom components have multifaceted orientation against bacterial, viral, fungal infections and other neuronal disorders. They can modulate the ion channels (K+, Na+, Cl−, Ca2+) of our body and this concept has been hypothesized in formulating pharmaceuticals. The triumphant achievement of these venom components as formulated anticancer agent in Phase I and Phase II clinical trials allure researchers to excavate beneficial venom components prohibiting DNA replication in malignant tumor cells. This review brings forth the achievements of Science and Technology in classifying the venom components as therapeutics and further application in drug product development.
Introduction
Science has always seized attention towards unusual things and if harvested, acts as a potent cure for human disorders. Poisonous, venom producing organisms, being a cause of mortality, have been a source of medicine to human syndrome since time immemorial. History says, in ancient Rome animal venoms were often used to diagnose smallpox, fever, leprosy and wound healing (Utkin 2015). One of the best contributions of animal venom in medical science is the discovery of bradykinin by Rocha e Silva and his team (Rocha e Silva et al. 1949) to reduce contraction of isolated guinea pig ileum upon incubating globulin fraction of dog plasma with snake venom (obtained from Bothrops jararaca). Arthropod envenomation is usually common during the summer months of the year due to increased agricultural activities (Bawaskar and Bawaskar 2012). They secrete venom in response to external stimuli to capture prey, survive from predators and hence build a dynasty on this planet. At optimum concentration, the venom finds application in the field of biotechnology to prevent and cure pharmacological disorders. Venom–toxins exert their effect by interacting with a range of targets which include cellular receptors, membranes, and ion channels. α-Bungarotoxin (venom component of elapid snake Bungarus multicinctus), a type of α-neurotoxin proves to be fatal when it binds irreversibly to nicotinic acetylcholine receptor, is one of the best examples of the application of toxin in medical research (Utkin 2015; Young et al. 2003). ‘Tumour Paint’ outlined by natural toxins or peptides from natural organisms (viz. scorpions) and fluorescent molecules by a bunch of scientists from Blaze Bioscience, Fred Hutchinson Cancer Research Centre and the University of Washington to interpret the whereabouts of cancer in the body.
Drug resistance, adverse drug reactions in patients have aroused in finding other alternatives for the better living condition of humanity. Investigation to generate derivatives of the active components of animal venoms is ongoing to implement them in the eradication or cure of human disorders. One such example is Kn2-7 obtained by substituting positively charged amino acids in scorpion venom peptide BmKn2 (Investigación y Desarrollo 2015). The climatic condition of the originating place is an essential factor influencing concentration and quality of toxins present in arthropods (Utkin 2015). Alteration in living conditions and venom extraction procedure tailors venom toxicity and composition (Utkin 2015). Emerging methods of proteomics and genomics evoke finding of newer compounds that aid in formulating alternative pharmaceuticals (Utkin 2015). Our review elaborates or rather praises the novelty of scorpion venom and its application in pharmaceutical science.
With the breakthrough in research and development in science and technology, novel approaches have been adopted to unveil venom toxins that do not bind antivenoms but can amalgamate to form venom immunization mixtures (Williams et al. 2011; Casewell et al. 2013). The discovery of Captopril (venom from Brazilian snake Bothrops jararaca) (Utkin 2015; Escoubas and King 2009), an ACE inhibitor used in the treatment of hypertension, was a remarkable discovery as it was the earliest success in using the concept of ligand-based drug design (Utkin 2015). Research has proven that venom from arachnids decreases risk of heart transplant (Utkin 2015). Blocking N-type calcium channel for analgesic activity is mediated by a venom peptide from snail Conus magus (Escoubas and King 2009).
About Scorpion Venom
Scorpions (Class: Arachnida, Order: Scorpiones) are predatory arachnids occupying terrestrial habitat except for Antarctica, of which Buthidae family characteristic of their triangular-shaped sternum is most widely studied and dangerous scorpion among all (Luna-Ramírez et al. 2015). In the earlier days of the twentieth century, scorpion oil had many applications in tumors, infections and inflammatory conditions (Podnar 2015). Incidence of scorpion envenomation is reduced in Asia though established reports hint southern India to be the most affected zone (Bawaskar and Bawaskar 2012). The venom is an amalgamation of peptides, proteins, nucleotides, and amines (Fig. 1) that has emerged as a curative to many disorders including cancer (Fig. 2). Often they lack enzymes in their venom except for Mesobuthus tamulus, Centruroides exilicauda and scorpions belonging to Heterometrus sp. (Gwee et al. 2002). The autonomic nervous system is perturbed during scorpion envenoming that elevate insulin and release glucagon, cortisol, angiotensin II (Krishnamurthy 2000). Scorpion venom toxins (SVTs) exert their pharmacological activities on human ion channels (Na+, K+, Ca2+, Cl−) (Kastin 2006) by blocking potassium and chloride channels (short chain peptides) or acting upon sodium and calcium channels (long chain peptides) (Smith et al. 2012; Petricevich 2010; Possani et al. 2000). Sodium channel acting toxins have shown to be most effective in mammals including humans (Ortiz et al. 2014). Venoms containing structurally diverse peptides with disulphide bridges exhibit multiple pharmacological properties and are very stable (Ortiz et al. 2014). The peptide mixture is known to trigger cell death (Ortiz et al. 2014) forming pores in biological membranes; a novel concept to destroy unwanted cells or initiate apoptosis.
