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Abstract Both mythologically and logically, snakes have always fascinated man. Snakes have attracted both awe and fear not only because of the elegant movement of their limbless bodies, but also because of the potency of their deadly venoms. Practically, in 2017, the world health organization (WHO) listed snake envenomation as a high priority neglected disease, as snakes inflict up to 2.7 million poisonous bites, around 100.000 casualties, and about three times as many invalidities on man. The venoms of poisonous snakes are a cocktail of potent compounds which specifically and avidly target numerous essential molecules with high efficacy. The individual effects of all venom toxins integrate into lethal dysfunctions of almost any organ system. It is this efficacy and specificity of each venom component, which after analysis of its structure and activity may serve as a potential lead structure for chemical imitation. Such toxin mimetics may help in influencing a specific body function pharmaceutically for the sake of man's health. In this review article, we will give some examples of snake venom components which have spurred the development of novel pharmaceutical compounds. Moreover, we will provide examples where such snake toxin-derived mimetics are in clinical use, trials, or consideration for further pharmaceutical exploitation, especially in the fields of hemostasis, thrombosis, coagulation, and metastasis. Thus, it becomes clear why a snake captured its symbolic place at the Asclepius rod with good reason still nowadays. [ABSTRACT FROM AUTHOR]

The receptor protein CLEC-2 on platelet membranes is the target of the endogenous ligand podoplanin found on cancer cells and of rhodocytin, a snake venom component of the Malayan pit viper Calloselasma rhodostoma. Ligand binding results in platelet activation, increased blood coagulation and thrombosis. In an effort to isolate rhodocytin, we have purified CLEC-2 as bait from E. coli. Affinity captured rhodocytin interacted with mammalian CLEC-2 and stimulated platelet aggregation in a dose dependent manner. [Display omitted] • Rhodocytin was isolated by affinity capturing using recombinant Clec-2. • Purified rhodocytin from Calloselasma rhodostoma interacted with mammalian Clec-2. • Affinity purified Rhodocytin triggered platelet activation and aggregation. [ABSTRACT FROM AUTHOR]

We report the cloning, full-length sequencing, and broad distribution of reptile-specific RPTLN genes across a number of Anapsida (Testudines), Diapsida (Serpentes, Sauria), and Archosauria (Crocodylia) taxa. The remarkable structural conservation of RPTLN genes in species that had a common ancestor more than 250 million years ago, their low transcriptional level, and the lack of evidence for RPTLN translation in any reptile organ investigated, suggest for this ancient gene family a yet elusive function as long noncoding RNAs. The high conservation in extant snake venom metalloproteinases (SVMPs) of the signal peptide sequence coded for by RPTLN genes strongly suggests that this region may have played a key role in the recruitment and restricted expression of SVMP genes in the venom gland of Caenophidian snakes, some 60-50 Mya. More recently, 23-16 Mya, the neofunctionalization of an RPTLN copy in the venom gland of snakes of the genera Macrovipera and Daboia marked the beginning of the evolutionary history of a new family of disintegrins, the α1β1-collagen binding antagonists, short-RTS/KTS disintegrins. This evolutionary scenario predicts that venom gland RPTLN and SVMP genes may share tissue-specific regulatory elements. Future genomic studies should support or refute this hypothesis. [ABSTRACT FROM AUTHOR]