Serine proteases are multifunctional and versatile venom components found in viper snakes, including the Bothrops species, a widely distributed genus notorious for causing the highest number of snakebites across Latin America. These enzymes, representing a significant fraction of Bothrops venom proteomes, exhibit a wide range of biological activities that influence blood coagulation, fibrinolysis, and inflammation. This review provides a comprehensive overview of serine proteases, with a particular focus on those found in the venom of Brazilian Bothrops snakes. The discussion begins with a summary of snake species found in Brazil and their medical relevance. Specifically addressing the Bothrops genus, this review explores the distribution of these species across Brazilian territory and their associated medical importance. Subsequently, the article investigates the biochemistry of Bothrops venoms and the clinical manifestations induced by envenomation. Finally, it offers an in-depth discussion on the serine proteases, highlighting their biochemical properties, mechanisms of action, and potential therapeutic applications. Furthermore, this review provides an in-depth exploration of the diverse serine proteases found in Bothrops venoms and their functional significance, from thrombin-like effects to potent fibrinogenolytic actions, which determine the clinical manifestations of envenomation. This review delves into the evolutionary adaptations and biochemical diversity of serine proteases in Bothrops venoms, emphasizing their critical roles in venom functionality and the resulting pathophysiological effects. Additionally, it opens new avenues for utilizing these enzymes in biomedical applications, underscoring their potential beyond toxinology.

Lancehead pitvipers, Bothrops snakes, or, popularly, “jararacas”, are common and broadly distributed in the Americas, especially in Brazil, where they are responsible for causing a high number of snakebite accidents. Their venoms are able to induce local and systemic effects, such as hemorrhaging, acute kidney failure, and shock, that can be fatal. Among the compounds of the venom are phospholipases A₂ (PLA₂s), which are abundant in some Bothrops species. PLA₂s can perform different activities during envenoming, such as neurotoxicity, myotoxicity, and cytotoxicity, among others, through the hydrolysis of the ester bond at the sn-2 position of phospholipids, producing free fatty acids and lysophospholipids. Although different PLA₂s can be classified into different PLA₂ groups and subgroups, according to structure, function, size, localization and Ca²⁺ dependence, they converge to be available in biotechnological and therapeutic applications, such as antiviral and antitumor, among others, being relevant molecules to be deeply studied. Here, we provide the state of the art of PLA₂s, found in snake venoms, focusing on Bothrops venoms, as well as their potential applications, beyond their inhibitors, that also receive attention due their importance in PLA₂ studies and diverse applications.

Leukemias and lymphomas are hematologic malignancies characterized by complex pathophysiological mechanisms and increasing global incidence. Despite advances in chemotherapy, immunotherapy, and targeted therapies, challenges such as drug resistance and relapse persist, necessitating novel therapeutic strategies. This review explores the cytotoxic potential of venoms derived from snakes, bees, and scorpions against leukemia and lymphoma cells. Numerous venom-derived components, such as L-amino acid oxidases (LAAOs), phospholipases A₂ (PLA₂s), and peptides like melittin, demonstrate selective antitumor activity through mechanisms involving oxidative stress, apoptosis induction, cell cycle arrest, and immunomodulation. These molecules exert their effects via mitochondrial pathways, caspase activation, and inhibition of pro-survival signaling cascades such as NF-κB and PI3K/Akt. Despite promising preclinical results, the clinical translation of these bioactive compounds remains limited due to challenges in standardization, delivery, and safety profiling. This review highlights recent advances in venom research, summarizes key molecular targets, and discusses future directions to harness venom-derived molecules as innovative therapies for hematological cancers.

Leishmaniasis and Chagas disease are neglected tropical diseases that continue to pose significant public health challenges, highlighting the need for new therapeutic strategies. Brazilian snake venoms represent a valuable and underexplored source of bioactive molecules with diverse pharmacological activities and promising therapeutic potential. In this context, the present study aimed to investigate the in vitro antiprotozoal potential of venoms from Bothrops and Crotalus species, including Bothrops jararacussu, Bothrops pauloensis, Bothrops alternatus, Bothrops leucurus, Bothrops atrox, Bothrops jararaca, Crotalus durissus terrificus, and Crotalus durissus ruruima, metalloprotease (MTL)- and crotoxin (CTX)-enriched, against Leishmania spp. and Trypanosoma cruzi. Crude venom protein profiles were analyzed by SDS-PAGE, and cytotoxicity was assessed in differentiated C2C12 myotubes and murine peritoneal macrophages. Antiprotozoal activity was evaluated against extracellular parasite forms, including promastigotes of Leishmania amazonensis and Leishmania infantum and epimastigotes of T. cruzi. Venoms exhibiting the highest selectivity indices (SIs), calculated using murine macrophage cytotoxicity data, were further tested against intracellular amastigotes of L. amazonensis. Among the tested samples, B. jararacussu venom showed activity against promastigotes of both L. amazonensis (IC₅₀ = 2.9 µg mL⁻¹) and L. infantum (IC₅₀ = 2.8 µg mL⁻¹), as well as in epimastigotes of T. cruzi (IC₅₀ = 15.5 µg mL⁻¹). The MTLand CTX pools from C. d. ruruima venom exhibited the highest activity against promastigotes of L. amazonensis, with IC₅₀ values of 1.6 and 3.8 µg mL⁻¹, respectively. Against intracellular amastigotes, MTL and CTX showed IC₅₀ values of 4.1 and 2.5 µg mL⁻¹, respectively, with selectivity indices (SIs) of 73.1 and 120, respectively. Overall, these findings provide preliminary evidence for the antiparasitic potential of snake venom-derived molecules, supporting further characterization and in vivo evaluation.