- A group of scientists discovered the mechanism by which cobra venom causes necrosis and have developed an antidote based on heparin | Photo by Anil sharma in Pixabay
Snakebites are estimated to kill around 138,000 people a year, mostly in sub-Saharan Africa and South and Southeast Asia. Now, a scientific team has discovered that a commonly used anticoagulant, heparin, can be used as a cheap antidote to cobra venom.
The “promising” research, which appears on the cover of the journal Science Translational Medicine, was carried out on cells and mice by scientists from the University of Sydney (Australia) and the Liverpool School of Tropical Medicine (England).
Cobras kill thousands of people worldwide each year and many more are severely maimed by venom necrosis (death of tissue and cells), which can lead to amputation. Current anti-venom treatment is expensive and does not effectively treat flesh necrosis, a statement from Sydney said.
Our discovery might dramatically reduce the horrific injuries caused by cobra bite necrosis and might slow down the venom, improving survival rates,” said Greg Neely of the Australian university.
Molecular dissection of venom
The team, which also includes scientists from Canada and Costa Rica, used CRISPR gene-editing technology to identify ways to block the venom of the red-necked and black-necked spitting cobra and was able to repurpose heparin and related drugs, showing that they can stop necrosis.
Researchers used CRISPR to find the human genes that cobra venom needs to cause necrosis. One of the targets cobra venom needs are the enzymes needed to produce the molecules heparan and heparin, which are found in many human and animal cells.
Heparan is found on the surface of cells and heparin is released during an immune response; their similar structure means that the venom can bind to both. The team used this knowledge to make an antidote capable of stopping necrosis in human cells and mice.
Unlike current methods for cobra bites, which use 19th-century technologies, heparinoid drugs act as a ‘decoy’ antidote. By flooding the bite site with heparin sulfate (decoy) or related heparinoid molecules, the antidote can bind to and neutralize the tissue-damaging toxins in the venom.
Three of the heparins used in the study are the same drugs currently used to prevent blood clots. All are already approved as anticoagulants, including the most effective heparinoid tested (tinzaparin), Nicholas Casewell of the Liverpool School of Tropical Medicine told EFE.
“Heparinoids are available for subcutaneous use, so we envision these molecules being injected close to the bite site in the community setting, where snakebite occurs.”
Currently, patients have to travel many hours to reach a hospital where they can receive antivenom treatment; “our hope is to be able to use heparinoids much earlier following a bite to reduce the severity of the envenomation,” adds Casewell.
For this researcher, the findings are interesting because current antivenoms are largely ineffective once morest severe local envenomation.
A challenge for the WHO
Snakebites kill up to 138,000 people a year and 400,000 more suffer long-term following-effects. Although the number of people affected by cobras is unclear, in parts of India and Africa, cobras account for the majority of snakebites.
The World Health Organization has identified bites from these reptiles as a priority in its program to combat neglected tropical diseases and announced the ambitious goal of halving the global burden of these bites by 2030.
The compounds do not require refrigeration like most antibody-based antivenoms, making heparinoids particularly useful in remote regions lacking medical infrastructure, the journal summarizes.
For now, there are no plans for a clinical trial with humans. “This is our hope for the next phase of this work, first we have to get funding (…),” Casewell told EFE, who nevertheless points out that heparin molecules have already been subjected to clinical trials for uses other than snake bites.
“Following the success of human trials, it might be rolled out relatively quickly and become a cheap, safe and effective drug for treating cobra bites,” concludes Tian Du of the University of Sydney.
With information from EFE
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2024-07-18 11:37:53
