Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury. According to new research, heparin, a commonly used blood thinner, can be repurposed as an inexpensive antidote for cobra venom.
The zebra snake (Naja nigricincta) in Namibia. Image credit: Wolfgang Wüster.
“Our discovery could drastically reduce the terrible injuries from necrosis caused by cobra bites — and it might also slow the venom, which could improve survival rates,” said University of Sydney’s Professor Greg Neely.
Using CRISPR gene-editing technology to identify ways to block cobra venom, the authors repurposed heparin and related drugs and showed they can stop the necrosis caused by cobra bites.
“Heparin is inexpensive, ubiquitous and a World Health Organization-listed Essential Medicine,” said University of Sydney Ph.D. student Tian Du.
“After successful human trials, it could be rolled out relatively quickly to become a cheap, safe and effective drug for treating cobra bites.”
The researchers used CRISPR to find the human genes that cobra venom needs to cause necrosis that kills the flesh around the bite.
One of the required venom targets are enzymes needed to produce the related molecules heparan and heparin, which many human and animal cells produce.
Heparan is on the cell surface and heparin is released during an immune response. Their similar structure means the venom can bind to both.
The scientists used this knowledge to make an antidote that can stop necrosis in human cells and mice.
Unlike current antivenoms for cobra bites, which are 19th century technologies, the heparinoid drugs act as a ‘decoy’ antidote.
By flooding the bite site with ‘decoy’ heparin sulfate or related heparinoid molecules, the antidote can bind to and neutralise the toxins within the venom that cause tissue damage.
“Our findings are exciting because current antivenoms are largely ineffective against severe local envenoming, which involves painful progressive swelling, blistering and/or tissue necrosis around the bite site,” said Liverpool School of Tropical Medicine’s Professor Nicholas Casewell.
“This can lead to loss of limb function, amputation and lifelong disability.”
The study was published in the journal Science Translational Medicine.
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Tian Y. Du et al. 2024. Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming. Science Translational Medicine 16 (756); doi: 10.1126/scitranslmed.adk4802
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