Snakebites, Venom & Heparin: Advancing treatment therapies

Snake usually bites to defend itself or capture its prey—a snake bites by piercing the skin with its fangs leading to injuries that may sometimes be potentially life-threatening.

Snakebites can be highly fatal due to toxins in the bite of venomous snakes. Each year around 1.8 million people get bitten by snakes out of which 138,000 lose their lives with 400,000 experiencing some sort of permanent disability.

The danger of snakebites

Snakes can be venomous as well as non-venomous. Some of the types of venoms that snakes carry include:

Haemorrhaging
Neurotoxins
Anti-clotting agents
Cytotoxins
Myotoxins

Snake venoms comprise various compounds typically targeting the tissue at exposure, the nervous system, and the heart.

The most frequent venomous snakebites are caused due to two types of snakes –

Coral Snakes
Pit vipers

Symptoms of snakebites depend on the type of venom however; a few common symptoms of venomous snakebites are:

Burning
Fang marks and severe pain at the bite site
Diarrhoea
Convulsions
Dizziness
Blistering
Nausea
Blurred vision
Fast pulse, and rapid heart rate
Difficulty breathing
Mental confusion
Paralysis and shock

Until now, research on snakebites has primarily focused on the category of the deadliest venoms. Hence the venoms that are comparatively less dangerous but can lead to long-term issues—have not received that much attention. Current treatment options for snakebites include antibody-based antivenoms which are not efficient in treating local tissue injury which is the prime cause of morbidity and are not readily available.

The Study

The team of researchers from the Liverpool School of Tropical Medicine in the UK, Instituto Clodomiro Picado in Costa Rica, and the University of Sydney, Australia investigated the options for treating snakebites.

How does the cobra venom work?

The study focused on the variety of cobras found in South Asia and Africa. The researchers isolated the venom from the African spitting cobra and ran a whole genome CRISPR screening.
Then with the help of CRISPR gene editing different genes were disabled across an entire human genome from a large mixture of human cells.
The modified cells when exposed to cobra venom which helped identify the cells that survived and the ones that died. This helped verify the cellular features necessary for lethality.
The researchers found that cobra venoms require heparan and heparin sulfate particular enzymes, to kill human cells.
These enzymes get released when the body’s immune system responds to a threat.

Heparin decoys for reducing damage

Heparin has been used for approximately one hundred years as medication for blood-thinning
On testing the drug on human cells, it was found that venoms did not cause cell death
Researchers tested the drug on distantly related Asian cobra which also showed a similar positive impact
After injecting a synthetic version of heparin (according to the medically recommended dose and route) called tinzaparin reduced the damage in mice with venom

How does heparin work?

The components of venom were divided to find out how heparin blocked the venom
The researchers discovered that heparin significantly inhibited ‘cytotoxic three-finger toxins’ that are majorly responsible for tissue damage
Until now, there were no drugs that worked against the toxins

Potentially cheaper and more accessible treatment for snakebites

The study involving the molecular dissection of cobra venom gave a brief insight into the better treatment options for snakebite envenoming. The study findings show that heparinoids are the possible inhibitors for three-finger cytotoxins.

Heparinoids are US FDA-approved blood thinning medications that are inexpensive and approved for self-administration as well. The characteristic of the drug being stable at room temperature makes it more accessible.