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The Next Generation of Venom Based Drugs

Healthcare | Dec, 2022

The contribution of natural products and their structural analogues have been astounding for pharmacotherapy. In recent years, several technological developments, and medical advances—including improved analytical tools, genome mining, microbial culturing—are opening new horizons for scientists to enable natural product-based drug discovery. Deadly venom from snakes, frogs, scorpions, and other animals is being used for the novel treatment of cardiovascular disease, cancer, and diabetes. Although a handful of drugs derived from venom are already available in the market, new research is enabling scientists to analyse and reproduce them in a lab.

Venom constitutes a cocktail of toxins that have evolved to be highly specific to molecules due to their stable cross-links in their structure. The high affinity and selectivity of venom makes scientists believe that it might be useful in targeting diseases. Some venom-derived drugs, such as captopril (isolated from the venom of Bothrops jararaca, a South American pit viper) and exenatide (obtained from one of the few venomous lizards, the Gila monster) are sold for chronic pain, autoimmune conditions, cardiovascular diseases, and cancer. Captopril was the first antihypertensive approved by the U.S. Food and Drug Administration (FDA) in 1981. Anybody taking high blood pressure medication are either taking captopril or one of its derivatives. Development of this toxin into a drug introduced a new class of medication, the ACE-inhibitors. Exenatide is the most recent venom-derived drug on the market, derived from the saliva of the gila monster. The venomous lizard does not eat more than three big meals a year, but their blood sugar levels remain stable. Hence, exenatide helps people with diabetes to produce their own insulin and lose weight. Only nine venom-derived drugs have been approved by the FDA.

With advances in genomics, proteomics, and transcriptomics, scientists are analysing the venom of even very tiny animals such as centipedes and assassin bugs.

Wasp Venom: Solution to Combat Antibiotic-Resistant Bacteria

Antibiotic resistance is one of the biggest healthcare challenges of our time. In United States, more than 2.8 million people get an antibiotic resistant infection, out of which 35,000 people lose their lives. Venoms represent untapped sources of novel drugs to combat multidrug-resistant pathogens. Researchers from Perelman School of Medicine at the University of Pennsylvania (Penn) have found molecules in wasp that have powerful antimicrobial and immunomodulatory properties that could lead to the discovery of new bacteria-killing drugs. These drugs would have the potential to combat antibiotic-resistant illnesses such as sepsis and tuberculosis. The researchers have engineered a highly small protein from common Asia wasp species, Vespula lewisii. The altered molecules have the ability to kill bacterial cells while reducing harm to the human cells. Although Mastoparan-L-containing venom is not dangerous to humans, it can trigger a type of inflammatory reaction that can make one susceptible to anaphylaxis.  

Chronic Pain Relief from Cole Snail Venom

Cole snail venom have proven to be effective for the treatment of severe pain, even for those patients who do not feel the effects of morphine. In March 2022, scientists have identified new cone snail toxin, which contains a compound, C.rolani that mimics a human hormone with a diverse set of biological functions. The snail activates two of the human receptors for somatostatin, which is generally an inhibitor of growth hormone and can be used to treat excessive growth disorder acromegaly. The chemical has demonstrated excellent analgesic properties in animal trials, and if the clinical trials go well, the venom-based drug could provide an alternative to opiates for managing chronic pain.

Through countless generation of predator-prey interactions, cone snails have created venoms that can be synthesized into drugs. Researchers are currently investigating the origin of Consomatin Ro1 in snails and understand the potential of the compound as an anti-inflammatory or pain reliever. They are looking forward to modifying the compound to make the venom even more useful for other medical needs.

Scientists are identifying a compound in the venom of auger snails, a close relative to cone snails, which have the potential to inhibit liver cancer proliferation and tumour size. The venom-based dug could alleviate the slate effects of chemotherapy, sparing the non-cancerous cells, which would be a medical breakthrough.

Snake venom as an anticancer agent

Snake venom is a rich source of natural bioactive compounds consisting of proteins, peptides, enzymes, and nucleotides. Purification of specific compounds can interfere with key tumorigenesis processes such as cancer cell invasion and metastasis. Some of these compounds have anticancer capabilities that have shown to possess selective toxicity for breast, cervical, and other cancer cells. Snake venom compound identified as being cytotoxic towards blood cancer cells include an LA00, which is purified from Calloselasma rhodostoma snake venom. The enzyme, MjTX-I is toxic towards leukaemia cancer cells, while being on-cytotoxic towards normal peripheral blood mononuclear cells. Snake-venom PLA2 enzymes are emerging as a viable treatment for blood cancers as well due to their excellent anticoagulant properties. Thus, discovery related to more such snake venoms could prove to beneficial for cancer patients and potentially lead to the development of novel, anticoagulant therapeutics.

Spider Venom to Treat Neurodegenerative Diseases

As incidences of neurodegenerative diseases is increasing, the discovery and development of new pharmacologically effective treatment strategies remains a focus for ongoing investigations. Age-related diseases are attracting more attention due to their high impact on healthcare systems. Hence, the negative impact of age-related disorders of the nervous system, including PD is on rise, and this disorder is expected to impact over 17 million people by 2040. Venom-derived products are offering a platform for the development of novel medicines, some of which are currently under clinical trial. Spider venom consists of a complex cocktail of compounds such as such as organic compounds, linear cytolytic peptides, disulfide-rich peptides (DRPs), and enzymes that act as neurotoxic cabals and synergistically target numerous types of neuronal membrane proteins such as receptors, ion channels, transporters, and enzymes. These compounds have been used to regulate pain and other neurological conditions. In clinical trials, no reports regarding concerns about safety issues of venoms have been found. However, venom side-effects that include allergy, hemorrhage, necrosis, or neurotoxicity etc. still remain a concern for scientists.

Way Ahead

Until relative recently, scientists had confined the study of venoms that came from snakes or lizards due to their high lethality. However, the emergence of sensitive analytical techniques and instruments has allowed researchers to turn their gaze towards smaller and smaller creatures and expand the catalogue of potential candidates. The pharmacological study of animal venoms still in the nascent stages as countless venomous creatures that inhabit the oceans are yet to be investigated. In coming years, more such venom-based drugs are expected to enter the market and advance medical field.