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.
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