Approaching the Golden Age of Natural Product Pharmaceuticals from Venom Libraries: An Overview of Toxins and Toxin-Derivatives Currently Involved in Therapeutic or Diagnostic Applications

Abstract

Poisons and the toxins found in venomous and poisonous organisms have been the focus of much research over the past 70 years, most of which has been directed at understanding the biochemical and physiological mechanisms by which they elicit their dramatic pathological consequences. Much knowledge has been gained in terms of how poisons and venoms and their composite toxins give rise to the syndromes associated with envenoming and poisoning and in some isolated cases there have been a few such agents promoted for therapeutic use. However, it has only been in the past decade that an explosion of interest has occurred in mining these natural, highly evolved libraries of bioactive toxins and poisons for use in pharmacotherapeutics as drugs or drug leads as well as in diagnostic applications. We ascribe this recent phenomenon to advances in toxinology which have provided investigators with a relatively thorough understanding of the nature of venoms and their biologically active toxins: particularly with regard to the peptidomes and proteomes of venoms. This is in conjunction with our greatly improved understanding of the etiology of many human diseases and the identification of sites of potential therapeutic intervention. In this review we provide an overview of some of the toxins, toxin derivatives or poisons from animal venoms and secretions which are in various stages of development for use as pharmaceuticals or diagnostics in human diseases. As one will recognize, developments in this field suggest that toxinology is now entering a golden age in terms of the identification and use of toxins as potent novel pharmaceuticals.

Dynamic evolution of venom proteins in squamate reptiles

“…For example, our data suggest that some physiological proteins present in members of the venomous reptiles may be a great source for investigation as new targets for drug discovery. A number of venom toxins have been successfully exploited for medical purposes as a result of their potent biological activities 28 . Toxin isoforms that have reverted back to a physiological function may share these functional potencies as a result of their common origin, yet have presumably subsequently evolved to be functionally non-toxic for expression in a vertebrate physiological system.…”

In Vitro Cytotoxic and Proapoptotic Activities of Anatolian Macrovipera Lebetina Obtusa (Dwigubski, 1832) Crude Venom on Cultured K562 Human Chronic Myelogenous Leukemia Cells.

“…7 A considerable number of bioactive proteins have been identified from snake venoms which have potential therapeutic value against various diseases such as cancer, bacterial and fungal infections, cardiovascular disorders (e.g., acute coronary syndrome) and arthritis. 5,6,[9][10][11][12][13][14] With a special focus on anticancer activity, various snake venoms and purified proteins (e.g., metalloprotease, disintegrin, PLA 2 , LAAO, CLP) have been shown to inhibit cancer progression in vitro and/or in vivo by affecting different cellular mechanisms, including apoptosis induction.…”

Centipede venoms as a source of drug leads

“…Many more venom-derived molecules that target an even wider range of disorders, including autoimmune disease, stroke and cancer, are in clinical and preclinical development [2][3][4][5][6][7][8][9][10]. Most of these molecules were derived from just a few well-studied venomous taxa [5,11], and therefore venoms remain an underutilized source of pharmacologically active compounds.…”