Drug Discovery Investigations of Reptile Venom

Nature endowed snakes with lethal venom, which they use to subdue prey and defend themselves. Venom proteins and peptides are of interest for drug discovery investigations.

크레스티드게코분양

Neurotoxins cause their prey’s muscles to stop working and suffocate, while haemotoxins disrupt blood clotting. Several compounds from snake venom have become potential pharmaceuticals.

How it Works

Snakes that have front fangs, such as adders and vipers, use venom to kill their prey. However, rear-fanged snakes like cobras and kraits use their venom for self-defense or to preserve food.

The venom of some snakes contains neurotoxic (nervous system-destroying) chemicals that interfere with nerve impulse transmission, and other toxins that attack the circulatory system and cause bleeding. Vipers have haemotoxic venoms, while elapids, which include cobras, mambas, and kraits, typically have venoms that are a combination of neurotoxic and haemotoxic.

In addition to these venom components, some snakes have proteins that can damage the skin and activate blood clotting systems. These are called anticoagulants.

The composition of viper venoms varies greatly among genera and individual species, with the 3FTx, PLA2 and SVSP enzymatic families making up 80% of the proteome in most viperids. The rest is a complex mix of other proteins, enzymes and peptides, such as C-type lectin and lectin-like proteins, defensins, natriuretic peptides and Kunitz-type serine protease inhibitors. Viperid venoms are also rich in anaphylactic proteins, which are capable of triggering a severe, potentially life-threatening allergic reaction in some people. Polyvalent antivenoms, designed to work on the venoms of multiple snake species, are available for treating viper bites. However, they must be matched to the type of venom that was injected in order to be effective.

Symptoms

Most snakes that bite humans are not venomous. Bites from nonvenomous snakes usually cause pain, swelling and bruising at the bite site which may spread down the arm or leg. A metallic taste in the mouth is common, and the person may experience headaches, chills, laboured breathing or a feeling of weakness. Some snakes, like coral snakes, have toxins that affect the nerves. They can cause tingling of the fingers and toes, and in severe cases a person may become weak, have trouble swallowing and faint.

The most important thing is to get to a hospital as quickly as possible after being bitten by a venomous snake. The victim should be moved as little as possible and covered with a clean, dry bandage to immobilize the bitten area. It is important not to raise the bitten limb above heart level as this increases absorption of the venom and accelerates the spread of envenoming.

The most effective treatment for a venomous snakebite is antivenom injection. It must be given as soon as possible, ideally within six hours of the bite. Antivenin is available at many hospitals in the United States and is very effective when administered early in the course of a snakebite. Some people who survive venomous snakebite will require skin grafts and rehabilitation to regain their independence, but death from a snakebite is rare with modern medical care.

Treatment

The availability of emergency medical care and antivenom will play a major role in how well a bitten victim does. If a person who has been bitten by a reptile is not immediately treated, they could experience serious venom effects, even from a bite that appears harmless at first glance.

The venoms of different snake species have remarkable biological complexity, which is only now being fully appreciated thanks to advances in transcriptomics and proteomics, along with other techniques like mass spectrometry, high-performance liquid chromatography and next-generation sequencing15. Using this information, scientists are discovering the incredible diversity of highly bioactive proteins and peptides in snake venom that recognize essential biological targets with exquisite specificity.

For example, a toxin from the viperid snake python (Pythonas jararaca) attacks the cytoplasmic membrane of muscle cells and triggers myotoxic cellular dysfunction. Its cellular target is a type of plasma membrane protein called a sarcolemma, which binds Ca2+ ions in muscle cells. This influx of ions starts a series of harmful events in the muscle cell that eventually leads to damage and degradation of the sarcolemma16.

Scientists are aiming to transform snake venom toxins into medicines that can be used to treat human diseases. Many compounds based on snake venom components are now in preclinical and clinical trials. Some are being developed with the aim of mimicking the toxin’s molecular recognition motifs, a route that promises cheaper, safer and orally available drugs.

Prevention

Snakes are a natural part of the environment and, while they do cause bites, it is generally not their intent to hurt people. If you are careful not to surprise them, and take certain preventative steps, you can minimize the threat of a bite.

Observe where you are going in the outdoors, especially after a rainstorm, and keep an eye out for any snakes trying to escape floodwaters or seek shelter from the weather. Never try to capture or kill a snake, and don’t reach into crevices or holes that you aren’t sure of – they may be hiding in there! Also, wear boots when hiking and long pants when spending time in the outdoors. These precautions can make a significant difference in the chance of a serious bite.

Be aware that even a non-venomous snake may bite a person, and some venomous bites do not produce any symptoms. Also, the venom composition of a given snake can change from a variety of factors including age, gender and prey availability.

If you do get bitten, remain calm and immobilize the area (splint the bitten limb or apply a tight band or tourniquet) as quickly as possible. Do not try to cut the wound and suck out the venom, or use electric shock, ice packs, herbal concoctions or black’snake stones’ on the bite, all of which can cause more problems than they solve.