In a groundbreaking scientific study, researchers from Sydney and Liverpool have discovered that a widely available blood thinner can serve as an antidote to cobra venom.
The research utilized CRISPR gene-editing technology to identify cells that are resistant to snake venom. These resistant cells were then used to determine the most effective method to prevent necrosis caused by snake bites.
The authors highlight snake bites as “the deadliest neglected tropical disease,” noting that they result in approximately 140,000 deaths annually and leave another 400,000 individuals permanently injured.
Snake venom varies, with cobra venom causing cell necrosis and also targeting the nervous system, heart, and brain.
Typically, antivenom costs about seven times the average daily wage in regions where cobra bites are most prevalent. Consequently, many pharmaceutical companies discontinue antivenom production due to cost issues.
By studying cobra venom—referred to by study author Professor Greg Neely as a “three-finger toxin”—on human cells, the team discovered a cell pathway present in all known animal species that produces the molecules heparan and heparin. Heparin is a commonly used blood thinner.
“Heparin is inexpensive, ubiquitous, and listed as an Essential Medicine by the World Health Organization. Following successful human trials, it could quickly become an affordable, safe, and effective treatment for cobra bites,” says Ph.D. student and lead author Tian Du, who, along with Professor Neely, works in functional genomics at the University of Sydney.
Heparin and heparan are both targeted by cobra venom. Heparan is found on cell surfaces, while heparin is released during immune responses. Due to their structural similarities, venom can bind to both, making the “heparan/heparin sulfate biosynthesis pathway” a major target. The red spitting cobra’s venom attacks 7 out of 11 components in this pathway, while the black-necked spitting cobra’s venom attacks 8 out of 11 components.
Using this knowledge, the team developed an antidote by using heparin to act as decoy molecules. This method protects endogenous heparin and the cells containing it by allowing the venom to attack the exogenous heparin instead. Cobras, part of the Elapidae family—which also includes sea snakes, mambas, and coral snakes—are responsible for more deaths and amputations in parts of Asia and Africa than any other snake group.
In an additional discovery, the team suggested that their method could be used to develop other antivenoms. Professor Neely explains in a video that venom types are limited across the animal kingdom, so cracking the code for one could accelerate the development of antivenoms for others. The three-finger toxins found in cobra venom are also present in the highly toxic bluebottle jellyfish of Australia, which is next on the team’s list for antivenom research.
When CRISPR technology first emerged, there were concerns it would be monopolized by wealthy nations for cosmetic and longevity treatments. It is inspiring to see CRISPR being used to benefit the world’s poorest and most vulnerable populations directly.