Some of the deadliest animals on earth are poisonous. Venom is their lethal weapon for self-defense or attack.
The toxin is injected into the skin and turns into poison. There are hundreds of lethal hypodermic syringes in nature. But it has a long history for humans to turn some of the most toxic substances on the earth into useful and even life-saving drugs.
For example, botulinum toxin, or Botox, can kill a million people with a dosage of 1g, but it can remove some wrinkles by paralyzing facial muscles. However, its role is not limited to this. In fact, botulinum was first used in the eyes Treatments for diseases such as crossed eyes and eyelid twitches, which are now also used to prevent migraine, are just one of many dreadful substances that have been fully utilized.
Increasingly, scientists are turning the most lethal substances in the animal kingdom into drugs that work well in very small amounts, in other words, they are ideal drugs. The molecular weight of animal toxin peptide is smaller than that of other toxins, and it has high specificity and molecular diversity.
It is directly encoded by genes and has low dosage but strong toxicity. It is the key physiological component acting on the target organism. Therefore, as a natural resource for drug research and development, animal toxin peptides are highly valued. A large number of drugs derived from animal toxin peptides have been approved by FDA for marketing, and some peptide drugs derived from animal toxins are still in clinical trials.
Snake venom polypeptide drugs
Many snake venom / peptide mixtures have been used in the treatment of snake venom mainly from a mixture of peptides and peptides.
Captopril, a pentapeptide compound extracted from Bothrops jaraca venom, is an enhancer of bradykinin. Captopril was synthesized by tailoring its structure and modifying ala Pro dipeptide. Captopril reduces blood pressure by increasing bradykinin activity and inhibiting thrombin (ACE). For the structural modification of captopril, enalapril, lisinopril, fosinopril and other drugs were developed successively.
Tirofiban, a peptide mimic of viper venom, is a antiplatelet drug, also known as glycoprotein IIb / IIIa inhibitor. Another antiplatelet drug, eptifibatide, was marketed almost at the same time as tirofiban.
It was a synthetic cycloheptapeptide, which was found in the venom of the southeastern Jurassic rattlesnake (Sistrurus miliariusb arbouri) and had a strong disintegrin effect. Studies have shown that the safety of etifebatide is slightly better than that of tirofiban in patients with acute coronary syndrome, but there is no significant difference in efficacy.
The oral anticoagulant ximelagatra, an oral anticoagulant from cobra venom, has been approved in some European and South American countries, but has not been approved by the FDA because elevated alanine aminotransferase (ALT) may increase the hepatotoxicity of the drug. Therefore, the development of the compound was stopped and withdrawn from the market in 2006.
Cenderitide from the venom of dendroapis angusticeps is the first toxic natriuretic peptide (NP) found. It has a certain inhibitory effect on the degradation of neutral endopeptidase. Preliminary clinical data show that cenderitide improves renal function. Patients with heart failure treated with cenderitide have completed a series of phase I and phase II trials, but researchers are concerned that the adverse effects of the drug may outweigh its benefits.
Ketongning injection (ketongning injection) and oral analgesic compound ketongning (klotril tablets), which are refined from cobratoxin extracted from cobra venom short chain α – neurotoxin of cobra snake venom, have the characteristics of strong analgesic effect, long duration of efficacy and low addiction. As high-efficiency analgesic drugs, ketongning has been used in clinical treatment for many years.
Recent studies have shown that cobra neurotoxin can produce central analgesia and high analgesia through adenosine A1 and A2 receptors, and its analgesic effect is stronger than that of morphine. In addition, cardiotoxin III (also known as cytotoxin III) isolated from Taiwan cobra venom can inhibit the migration and invasion of MDA-MB-231 breast cancer cells without causing cell apoptosis or cell cycle arrest.
Hemocoagulase Agkistrodon is a kind of double chain snake venom thrombin (svtle). It has good hemostatic activity, safety and little side effects. It is listed as a national first-class drug (suling) in China. Phase III clinical trials show that it has good coagulation and hemostatic functions.
Scorpion toxin peptide drugs
Scorpion is a valuable resource of traditional Chinese medicine in China. Traditional Chinese medicine believes that scorpion has the functions of calming the wind, relieving spasm, dredging collaterals, relieving pain, attacking toxin and dispersing mass. It is mainly used in the diagnosis and treatment of convulsion, epilepsy, spasm, stroke, tetanus and cancer.
Scorpion venom, which exists in the gland tissue of scorpion tail, has complex components, including neurotoxins, cytotoxic peptides, proteases and other toxic components. It is a kind of protein or peptide mixture with multiple biological activities. The specific binding of these toxins to ion channels can block the channel current or change the gating kinetics, thus changing the permeability of cell membrane.
It was found in the venom of scorpion leiurus quinquestriatus that Chlorotoxin peptide could delay the activity of human glioma cells in vitro. The venom of the Venezuelan scorpion Tityus dispans has antibacterial and antiparasitic activities, and can inhibit the growth of Leishmania in vitro. Bengalin, a toxin protein of Indian black scorpion, can induce apoptosis of human leukemic cells and improve biochemical indexes of osteoporosis in female rats in vitro.
The α – neurotoxin found in scorpion venom can delay the inactivation of sodium channel at neuromuscular junction, which may enhance neuromuscular reflex and airway contraction, which can theoretically treat sleep apnea.
Anemone toxin peptide drugs
Sea anemone is one of the oldest poisonous animals in existence. Sea anemone, like other members of the phylum spinosa, has many special spines, which are widely distributed throughout the body. SHK toxin isolated from anemone is an effective Kv1.3 channel blocker.
Kv1.3 channel plays an important role in the activation of human effector memory T cells (proliferation and cytokine production). SHK can treat T cell-mediated autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Kv1.3 receptor blockers are also considered as targets for the treatment of obesity.
SHK toxin also has potential applications in the treatment of obesity and insulin resistance. Shk-186 is an analogue of SHK toxin, now known as dalazatide drug. It has successfully completed clinical trials and entered the drug market for the treatment of autoimmune diseases.
Hirudotoxin polypeptide drugs
Leech is an important traditional Chinese medicine, which can treat cerebral hemorrhage and other thrombosis related diseases. Hirudin is an effective anticoagulant in the salivary glands of leeches.
Hirudin can inhibit the formation of thrombus and prevent blood coagulation of host. Pharmacological studies have shown that hirudin has anticoagulant, antithrombotic, anti atherosclerotic, anti platelet aggregation, anti-tumor, anti-inflammatory, improving Hemorheology and protecting cerebral ischemia-reperfusion injury.
Hirudin based anticoagulants include recombinant hirudin (lepirudin and Desirudin) and hirudin analogue bivalirudin. Lepirudin was approved by FDA to treat heparin associated thrombocytopenia (HIT) and related thromboembolic diseases, but was withdrawn in 2012 for commercial reasons.
Diirudin has been approved by FDA for the prevention of deep venous thromboembolism (DVT) after hip joint or for knee arthroplasty. Bivalirudin has been approved by FDA for the treatment of unstable angina pectoris after percutaneous coronary intervention (PCI), and the risk of hit or hit is increased.
However, the use of these thrombin inhibitors has several disadvantages, such as bleeding, strong dependence on renal function, lack of antidote and rebound of hypercoagulable state. Therefore, it is urgent to develop efficient and safe derivatives of hirudin.
Although a large number of animal toxins have not yet been developed, great achievements have been made in the clinical application of animal toxin peptide drugs, which makes more people realize the great potential and Prospect of animal toxin peptide drug research and development.
However, the effectiveness and safety of many animal toxin drugs in clinical treatment need to be further verified. Therefore, drug research and development based on animal toxins also has great challenges.
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