Scientists say they have discovered an antidote to the sting delivered by the box jellyfish Chironex fleckeri, which is considered to be one of the most venomous animals on Earth. The antidote blocks the symptoms of a box jellyfish sting if administered to the skin within 15 minutes after contact; it was shown to suppress tissue necrosis and pain in mice and to work on human cells outside the body.
Chironex fleckeri. Image credit: Guido Gautsch / CC BY-SA 2.0.
Commonly known as the sea wasp, Chironex fleckeri has about 60 tentacles that can grow up to 10 feet (3 m) long.
Each tentacle has millions of microscopic hooks filled with venom — a mixture of bioactive proteins that can cause potent hemolytic activity, cytotoxicity, membrane pore formation and inflammation.
A single sting to a human will cause necrosis of the skin, excruciating pain and, if the dose of venom is large enough, cardiac arrest and death within minutes.
University of Sydney’s Dr. Greg Neely and colleagues used the gene-editing tool CRISPR-Cas9 to identify how the Chironex fleckeri venom works.
“We were looking at how the venom works, to try to better understand how it causes pain,” Dr. Neely said.
“Using new CRISPR genome editing techniques we could quickly identify how this venom kills human cells.”
“Luckily, there was already a drug that could act on the pathway the venom uses to kill cells, and when we tried this drug as a venom antidote on mice, we found it could block the tissue scarring and pain related to jellyfish stings. It is super exciting.”
The study authors took a vat of millions of human cells and knocked out a different human gene in each one.
Then they added the Chironex fleckeri venom and looked for cells that survived.
From the whole genome screening, they identified human factors that are required for the venom to work.
“The jellyfish venom pathway we identified in this study requires cholesterol, and since there are lots of drugs available that target cholesterol, we could try to block this pathway to see how this impacted venom activity,” said first author Dr. Raymond (Man-Tat) Lau, also from the University of Sydney.
“We took one of those drugs, which we know is safe for human use, and we used it against the venom, and it worked. It’s a molecular antidote.”
“Our antidote is a medicine that blocks the venom. You need to get it onto the site within 15 minutes. In our study, we injected it. But the plan would be a spray or a topical cream,” Dr. Neely said.
“We know the drug will stop the necrosis, skin scarring and the pain completely when applied to the skin. We don’t know yet if it will stop a heart attack. That will need more research and we are applying for funding to continue this work.”
The discovery is described in a paper published online April 30 in the journal Nature Communications.
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Man-Tat Lau et al. 2019. Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote. Nature Communications 10, article number: 1655; doi: 10.1038/s41467-019-09681-1
