For the deadliest animals on earth, venom is their deadly weapon. They use venom to defend themselves or attack predators. There are hundreds of animals in nature with hypodermic syringes that can inject venom. However, humans have a long history of transforming some of the most toxic substances on the planet into useful and even life-saving drugs. For example, botulinum toxin, namely Protox, is enough to kill one million people in an amount of 1g, but it can remove wrinkles by numbing facial muscles. Botox was first used to treat eye diseases, such as crossed eyes and eyelid twitches, and is now also used to prevent migraines. It is just one of many toxic substances that have been fully utilized. Scientists are increasingly turning the deadly substances in nature into medicines. Only a small amount of these substances can be used to achieve good therapeutic effects. In other words, they are very ideal drugs.
Peptide drug from snake toxin
Snake venom is a mixture mainly composed of enzymes and non-enzymatic proteins/peptides. Many drugs derived from snake toxin peptides have been used in clinical treatment. A pentapeptide compound extracted from the venom of the Brazilian agkistrodon Bothrops jaracaca is an enhancer of bradykinin. By tailoring the structure of the pentapeptide compound and modifying the dipeptide of the smallest pharmacophore Ala-Pro, an oral drug “Captopril” can be synthesized. Captopril reduces blood pressure by increasing bradykinin activity and inhibiting thrombin (ACE), and is a conventional drug for the treatment of hypertension. By modifying the structure of Captopril, Enalapril, Lisinopril, Ramipril, Fosinopril and other drugs have been developed. Ximelagatra, an oral anticoagulant derived from cobra venom, is a vitamin K antagonist. It has been approved in some European and South American countries, but the FDA has not approved it for marketing because the increase in alanine aminotransferase (ALT) may enhance the toxic effects of drugs. Recent studies have shown that cobra neurotoxin can produce analgesic effects through adenosine A1 and A2 receptors, and its analgesic effect is stronger than morphine. Hemocoagulase Agkistrodon is a double-stranded snake venom thrombin (svTLE), which has good hemostatic activity and low side effects. Its phase III clinical trials have shown that it has good coagulation and hemostasis functions.
Peptide drug from Scorpion toxin
Scorpion venom exists in the venom gland tissue of the scorpion tail and contains neurotoxins, cytotoxic peptides, proteases and other toxic components. It is a mixture of proteins or peptides with multiple biological activities. The specific binding of these toxins with ion channels can block the channel current or change the gating dynamics, thereby changing the permeability of the cell membrane. The chlorotoxin peptide in the venom of Leiurus quinquestriatus can delay the activity of human glioma cells in vitro. The toxin protein Bengalin of the Indian black scorpion can cause the apoptosis of human leukemia cells in vitro and the improvement of the biochemical indicators of osteoporosis in female rats.
Peptide drug from Sea anemone toxin
Like other members of the Cnidaria phylum, sea anemones have many special stinging cells that are widely distributed throughout the body. The ShK isolated from sea anemones is an effective Kv1.3 channel blocker, which is essential for the activation of human effector memory T cells. ShK can treat T cell-mediated autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. Kv1.3 receptor blockers are also considered to be targets for the treatment of obesity. ShK-186 is an analogue of ShK and is now called Dalazatide. It has now successfully completed clinical trials and entered the drug market for the treatment of autoimmune diseases.
Peptide drug from Hirudin toxin
There is an effective anticoagulant-hirudin in the salivary glands of leeches. Hirudin can inhibit the formation of thrombus and prevent blood clotting. Pharmacological studies have shown that hirudin has the functions of anticoagulation, antithrombosis, anti-atherosclerosis, anti-platelet aggregation, anti-tumor, anti-inflammatory, improving hemorheology, and so on. Hirudin-based anticoagulants include recombinant hirudin (Lepirudin and Desirudin) and its analog Bivalirudin. Lepirudin was approved by the FDA for the treatment of heparin-related thrombocytopenia (HIT) and related thromboembolic diseases, but was withdrawn in 2012 due to commercial reasons. Disirudin is approved by the FDA to prevent deep vein thromboembolism (DVT) behind the hip joint. Bivalirudin is approved by the FDA for the treatment of unstable angina pectoris after percutaneous coronary (PCI) intervention.
Although there are still a large number of animal toxins that have not yet been developed, great achievements have been made in clinical application of animal toxin peptide drugs. Therefore, more people have realized the great potential and prospects of the research and development of animal toxin peptide drugs. However, the effectiveness and safety of many animal toxin drugs in clinical treatment still need to be further verified. The research and development of animal toxin-based drugs is facing great challenges.