Snakebite envenoming is a neglected tropical disease causing approximately 81,410–137,880 deaths globally each year and four-fold more disabilities than mortality rate. Despite the availability of antivenoms for treatment, several in vitro and in vivo preclinical studies have shown that their efficacy is limited by many factors including regional venom variation and poor neutralization of major venom toxins. To address these limitations, the potential of alternatives including aptamers, recombinant monoclonal antibodies, camelid antibodies, small molecule inhibitors, and natural product-based inhibitors targeting key venom proteins have been explored. Among these, small molecule inhibitors targeting key enzymatic snake venom proteins are emerging as adjuvants to antivenom treatment. Most of these small molecules are repurposed drugs with established safety, oral bioavailability, and lower cost compared to antivenoms. In this regard, this review tries to compile available information regarding the use of small molecule inhibitors to counteract envenomation with special emphasis on three major enzymatic snake venom protein families: phospholipase A₂, snake venom metalloproteinases, and snake venom serine proteases. In vitro studies have shown that these small molecule inhibitors used either alone or in combination with antivenom can potentially reduce the adverse effects of venom-induced coagulopathy, neurotoxicity, tissue damage, and inflammation. However, critical gaps remain including limited human clinical trial data, uncertain efficacy across diverse venoms, and undefined dosing strategies. Overall, small molecules represent a mechanistically targeted and clinically promising adjunct to antivenom therapy, warranting further validation through randomized trials, pharmacokinetic studies, and development of field-applicable treatment protocols.

Snake 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.