Researchers at the University of Sydney and Liverpool School of Tropical Medicine have unveiled a groundbreaking finding: a commonly used blood thinner, heparin, can now be repurposed as a cost-effective antidote for cobra venom.
Cobras cause fatalities globally each year, with countless more suffering severe tissue damage known as necrosis due to the venom, sometimes resulting in limb amputation.
The current antivenom treatment is costly and does not effectively address the necrosis at the bite site.
“Our breakthrough could significantly reduce the severe tissue damage from cobra bites, and potentially increase survival rates by slowing down the venom,” stated Professor Greg Neely, a key researcher from the University of Sydney.
Through the use of CRISPR gene-editing technology to discover methods to counteract cobra venom, a team of international scientists successfully repurposed heparin, a common blood thinner, and related medications to halt the necrosis caused by cobra bites.
Their research has been featured on the cover of Science Translational Medicine.
Lead author Tian Du, a PhD student also from the University of Sydney, remarked, “Heparin is widely available, affordable, and listed as an Essential Medicine by the World Health Organization. Following successful human trials, this treatment could be swiftly implemented as a low-cost, safe, and efficient solution for cobra bites.”
By utilizing CRISPR, the team pinpointed the human genes required by cobra venom to induce necrosis in the surrounding flesh of the bite. One of these necessary venom targets are enzymes essential for the production of heparan and heparin, compounds that numerous human and animal cells generate. Both heparan and heparin bear a resemblance in structure, allowing the venom to bind to them. Leveraging this knowledge, the team developed an antidote capable of halting necrosis in human cells and mice.
Unlike conventional antivenoms for cobra bites, which are outdated technologies, the heparinoid drugs function as a ‘decoy’ antidote. By saturating the bite area with ‘decoy’ heparin sulfate or similar heparinoid molecules, the antidote can attach to and neutralize the venom toxins responsible for tissue damage.
Joint corresponding author Professor Nicholas Casewell, Head of the Centre for Snakebite Research & Interventions at Liverpool School of Tropical Medicine, highlighted, “Snakebites remain a significant health threat among neglected tropical diseases, predominantly affecting rural populations in low- and middle-income countries.”
“Our discovery is promising as current antivenoms often fall short in combatting severe local envenoming, characterized by painful swelling, blistering, and tissue necrosis in the vicinity of the bite. This can lead to loss of limb function, amputation, and lifelong impairment,” added Professor Casewell.
Snakebites claim around 138,000 lives annually, with an additional 400,000 individuals enduring long-term repercussions from the bite. Although the exact number of cobra-related incidents is uncertain, these species are responsible for numerous snakebite incidents in certain regions of India and Africa.
The World Health Organization regards snakebite as a priority within its neglected tropical diseases initiative, setting an ambitious target to halve the global snakebite burden by 2030.
Professor Neely expressed, “With this deadline approaching in just five years, we believe that our new antidote for cobras can contribute to the global efforts to minimize fatalities and injuries from snakebites in some of the most underserved communities worldwide.”
Operational in the Dr John and Anne Chong Laboratory for Functional Genomics at the Charles Perkins Centre, Professor Neely’s team employs a systematic approach to identify treatments for venomous bites. They utilize CRISPR to identify genetic targets that venoms or toxins exploit in humans and other mammals, developing strategies to thwart these actions and ideally shield individuals from the harmful effects of these venoms.
This strategy was previously instrumental in identifying an antidote to box jellyfish venom by the team in 2019.
Professor Casewell oversees the Centre for Snakebite Research & Interventions at Liverpool School of Tropical Medicine (LSTM), which has been conducting diverse research activities for over 50 years to comprehend snake venom biology and enhance the efficacy, safety, and affordability of antivenom treatments for tropical snakebite victims. The center houses some of the world’s top experts in snakebites and has access to LSTM’s herpetarium, containing the UK’s largest and most diverse collection of tropical venomous snakes.
