Are you venomous? Don't be afraid! Scientists have found a "cheap antidote" for cobra venom

Compiled by: Gong Zixin

Cobra bites kill thousands of people worldwide each year, and more than 100,000 people are severely disabled due to the tissue and cell death caused by their venom. However, current antivenom treatments are expensive and cannot effectively treat necrosis at the site of the bite.

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Scientists have made a remarkable discovery:

Heparin, a commonly used blood thinner

Could be used as a 'cheap antidote' for cobra venom

Can prevent necrosis

Potentially saving thousands of lives each year

A team of scientists from Australia, Canada, Costa Rica and the United Kingdom used CRISPR gene editing technology to identify a way to block cobra venom, successfully repurposing heparin (a common blood thinner) and related drugs, and showed that they could prevent necrosis caused by cobra bites. The related paper was published on the cover of Science Translational Medicine on July 17.

"Our findings could significantly reduce the horrific necrosis caused by cobra bites and potentially slow the release of venom, thereby improving survival rates," said senior author Professor Greg Neely from the Charles Perkins Centre and Faculty of Science at the University of Sydney.

The researchers noted that heparin is inexpensive, ubiquitous and listed as an essential medicine by the World Health Organization. After successful human trials, it could be introduced relatively quickly as a cheap, safe and effective treatment for cobra bites.

The research team took a systematic approach to finding drugs to treat deadly or painful venoms. They used CRISPR to identify the gene targets used by venoms or toxins in humans and other mammals, and then used that knowledge to design ways to block that interaction, ideally protecting people from the deadly effects of these venoms. The team previously used this approach in 2019 to identify an antidote for box jellyfish venom.

In vitro genome-wide CRISPR-Cas9 KO screen identifies genes required for cytotoxicity of African spitting cobra venom

Heparin and LMW heparin block the effects of Naja venom in vitro

In this study, scientists used CRISPR technology to find the human genes required for cobra venom to cause necrosis of the flesh around the bite. One of the desired venom targets was an enzyme required to produce the related molecule heparin and heparin, which many human and animal cells produce. Heparin is on the surface of cells and is released during immune responses. Their similar structures mean that the venom can bind to both. The team used this knowledge to create an antidote that blocked necrosis in human cells and mice.

Unlike current antivenom for cobra bites (a 19th century technology), the heparinoid drug is a "decoy" antidote. By injecting a "decoy" heparan sulfate or related heparinoid molecule into the bite site, the antidote can bind to and neutralize the toxins in the venom that cause tissue damage.

Snake venom-induced endometrial disease is inhibited in vivo by heparinoids

Co-corresponding author Professor Nicholas Casewell, Director of the Snakebite Research and Intervention Centre at the Liverpool School of Tropical Medicine, noted that snakebites remain the most deadly of neglected tropical diseases, with the burden falling mainly on rural communities in low- and middle-income countries.

"Our findings are exciting because current antivenoms are largely ineffective against severe local envenomations, which include painful, progressive swelling, blistering, tissue necrosis around the bite site, which can lead to loss of limb function, amputation, and lifelong disability."

Snake bites kill up to 138,000 people each year, and another 400,000 suffer long-term illnesses from snake bites. While the number of people affected by cobras is unknown, they are responsible for most snake bites in parts of India and Africa.

WHO has elevated snakebite to a Priority A Neglected Tropical Disease and announced an ambitious target to halve the global burden of snakebites by 2030.

Professor Neely said: "With only five years left to go, we hope our discovery of a new cobra antidote can help reduce death and injury from snake bites in some of the world's poorest communities."