Ribbon worm venom potential weapon against malaria

From the world's longest animal, the nemertine – also known as ribbon worm – which can reach up to 50 meters, Uppsala University's research group in pharmacognosy have succeeded in extracting an extremely toxic peptide, naming it alpha-nemertides. One gram of its archetype, nemertide alpha-1, is enough to kill 1,000 tons of cockroaches, and in a new PhD thesis, Quentin Laborde presents additional findings about the peptide's potential in the development of drugs and bio-pesticides.

“In order for nemertid alpha-1 to have the intended effect against cockroaches, injections are required. Thus, my project began as an attempt to identify a more effective method. Quite early in the process, we discovered a new family of peptide toxins in the skin mucus of a worm in the North Sea, whose archetype proved to be 30 times more potent against pests and with a lesser impact on common pollinators, such as the eastern bumblebee," says Quentin Laborde, PhD student at the Department of Pharmaceutical biosciences.

With the newfound peptide in safe custody, focus once more turned towards alpha-nemertides, and through chemical studies, Quentin Laborde was able to identify five positions in the amino acid sequence that are central to its toxicity – a result paving the way to recreate the peptide with increased selectivity and potency against the pests to be controlled. Another important conclusion is that the peptide via one single amino acid mutation can be targeted towards mammals. Thereby improving its relevance for the development of new drugs and pharmacological tools.

“We also saw that nemertide alpha-1 prevents green peach aphids from eating, which can make it an effective tool to protect plants against pests. In yet another study, we mixed nemertide alpha-1 in blood before making it available to two mosquito species that carry the Zika virus and malaria parasites. When the mosquitoes sucked the blood, they were quickly paralyzed before dying within a day, an effect that makes this peptide an interesting lead in the fight against several insect-borne diseases,” states Quentin Laborde.

The thesis also opens up several interesting possibilities for further research. These include deeming nemertide alpha-1 as harmless to humans with only a weak toxicity on human cells and potential to store for longer periods of time. Ulf Göransson, Professor of Pharmacognosy, pinpoints, among many things, the possibility to modify the peptide in order to govern its functions in the human body, which in turn might provide a catalyst in the development of new drugs against epilepsy, pain and other conditions.

“The peptides that Quentin have studied are among the most toxic substances we have encountered and now we will continue this journey within the framework of Biodiversity2Drugs, where we together with researchers in 13 European countries will map the possibilities to utilize nemertide alpha-1 in different organisms. Add the fact that nearly 95 percent of all nemertine species remain to be explored in terms of poison, and it sums up to a very interesting future,” says Ulf Göransson.

text: Magnus Alsne, photo: Mikael Wallerstedt, Stefan Verheyen