Biomedical applications of snake venom: from basic science to autoimmunity and rheumatology

Abstract

Snake venoms have components with diverse biological actions that are extensively studied to identify elements that may be useful in biomedical sciences. In the field of autoimmunity and rheumatology, various findings useful for the study of diseases and potential drug development have been reported. The study of disintegrins, proteins that block the action of integrins, has been useful for the development of antiplatelet agents and principles for the development of immunosuppressants and antineoplastics. Several proteins in snake venoms act on the coagulation cascade, activating factors that have allowed the development of tests for the study of coagulation, including Russell’s viper venom time, which is useful in the diagnosis of antiphospholipid syndrome. Neurotoxins with either pre- or postsynaptic effects have been used to study neurogenic synapses and neuromuscular plaques and the development of analgesics, muscle relaxants and drugs for neurodegenerative diseases. Various components act by inhibiting cells and proteins of the immune system, which will allow the development of anti-inflammatory and immunosuppressive drugs. This review summarizes the usefulness of the components of snake venoms in the fields of autoimmunity and rheumatology, which can serve as a basis for diverse translational research.

Snake Venoms in Diagnostic Hemostasis and Thrombosis

“…Snake venom thrombin-like enzymes (SVTLEs) have been identified in over 30 species of snake, predominantly in viper venoms. 7,24 In contrast to thrombin, which cleaves both the α and β chains of fibrinogen to promote fibrin polymerization, SVTLEs are typically selective and usually cleave only one of the chains. 7,15 Most SVTLEs release only fibrinopeptide A (FPA), and are termed venombin A enzymes, while there are examples that release only fibrinopeptide B (venombin B), and a few that act on both α and β chains (venombin AB).…”

“…None of the SVTLEs exhibit the multiplicity of function of thrombin, so most do not activate FXIII or protease-activated receptors on platelets. 7,16,24 The lack of cross-linking results in unstable clots in vivo that are readily destroyed by plasmin, ultimately leading to a consumptive coagulopathy that depletes fibrinogen. Consequently, SVTLEs have been used as rapid therapeutic defibrinating agents in the anticoagulant management of vascular disorders such as acute ischemic stroke.…”

“…Other than insensitivity to thrombin inhibitors, reptilase/batroxobin times tend to be elevated in situations that prolong TT, such as reduced fibrinogen concentration or function, defective fibrin polymerization, and elevated fibrin(ogen) degradation products (FDPs). 24 If TT is more elevated than reptilase/batroxobin time is, the presence of FDPs is indirectly indicated. 24,28 Although not necessary when investigating for dysfibrinogenemia, 29 TT and reptilase/batroxobin time can be used as screening tests, as they are frequently prolonged, and can be used to distinguish between α and β chain variants.…”

“…24 If TT is more elevated than reptilase/batroxobin time is, the presence of FDPs is indirectly indicated. 24,28 Although not necessary when investigating for dysfibrinogenemia, 29 TT and reptilase/batroxobin time can be used as screening tests, as they are frequently prolonged, and can be used to distinguish between α and β chain variants. 30,31 An interesting quirk with reptilase/batroxobin times is that the elevated fibrinogen in an acute phase reaction can paradoxically prolong them but not TT, giving rise to the possibility of a false diagnosis of a dysfibrinogenemia.…”

Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases

“…The largest and most investigated family of disintegrins is the RGDdisintegrins [53,54]. Several disintegrins were isolated from snake venoms especially from viper venom and described as antithrombotic agents [55]. Trigramin, a disintegrin containing the RGD (Arg-Gly-Asp) sequence purified from the venom of the common bamboo viper (Trimeresurus gramineus), was shown to inhibit platelet aggregation in vitro and in vivo by blocking fibrinogen binding to aggregation agonist-stimulated platelets like fibrinogen binding ADP-activated platelets [56,57].…”