Neither a tarantula’s painful bite nor a sea snail’s lethal sting sound all that pleasant – or useful – for humans.
But venom from the poisonous pair could lead to next-generation painkillers, thanks to a group of scientists from Australia’s University of Queensland. They discovered how a toxin found in a tarantula’s venom delivers its blow, and with that knowledge created a promising new drug candidate to treat chronic pain.
To catch a fast-moving meal, venomous animals such as the tarantula sting, injecting a cocktail of paralysing peptides into their prey. At molecular scale, these peptides find and dock to tiny so-called “sodium ion channels” dotted along the outer membrane of nerve cells.
Some of these channels are responsible for transmitting nerve signals to muscles. Once the venom peptides are latched on, nerve cells stop firing, preventing prey from moving or escaping.
But not all channels are the same – some are only responsible for transmitting pain signals to the brain. This has prompted scientists to develop venom peptides as chronic pain medication. The key is making it selective – a new painkiller is little use if it ends up paralysing a patient.
The Queensland team analysed and modelled how a toxin from the Peruvian green velvet tarantula, called ProTx-II, docks to its channel target.
The team’s data suggests that before the peptide locks on, it’s “sucked in” by the molecules in the membrane around the channel. Only when several peptide molecules congregated, simulations showed, did the peptides locked in the right orientation to block their target channel.
“Our results show that the cell membrane plays an important role in the ability of ProTx-II to inhibit the pain receptor,” author Sónia Troeira Henriques said.
Using this information, the team are now designing potential drugs that are more likely to find a painkilling target.
The researchers started by modifying a peptide called MfVIA, isolated from the venom of the predatory sea snail Conus magnificus, known as the “magnificent cone”.
The team synthesised modified versions of the sea snail peptide, designed to latch more strongly to the area around its ion channel target. One of these new peptides “showed a striking improvement in selectivity” over other channel types, the authors stated.
The peptide has also already been effective in treating pain in animal models, the team added. The findings were presented in the Biophysical Society’s 60th Annual Meeting.