Hemostasis-Modulating Proteins from Indian Elapid and Viper Snake Venom: Mechanistic Insights and Therapeutic Opportunities
Shanmugaraja Kiruthika, Aaron Varghese Sanju, Sameer Basha Hussain, Bipin Gopalakrishnan Nair, Muralidharan VanuopadathSnake venom is a complex cocktail of biologically active proteins and peptides with highly specific physiological activities, yet its therapeutic potential remains largely unexplored. India is home to several snake species, including vipers and elapids. Though viper venom is predominantly associated with hemostatic manifestations, several elapids can also disrupt hemostasis and cause venom-induced consumption coagulopathy. Snake venom protein families, including snake venom metalloproteases, serine proteases, phospholipases, disintegrins, snaclecs, L-amino acid oxidases, nucleotidases, and three-finger toxins, are involved in modulating the hemostatic system. In this review, we compile the available information on hemostasis-altering proteins from Indian elapids and vipers that have specific impacts on platelet aggregation and intrinsic, extrinsic, and common coagulation pathways. The molecular mechanisms of venom proteins in coagulation and platelet aggregation pathways are briefly discussed in relation to their functional consequences. Further, some of the venom proteins that are considered potential therapeutic leads targeting thrombotic disorders based on their mechanistic similarity with existing venom-derived and FDA-approved drugs are discussed. Overall, this review is focused not only on the mechanism of action behind the hemostatic-intervening proteins but also on their efficiency to develop novel therapeutics to treat thrombotic disorders.