Nav: Home

New drug against nerve agents in sight

May 03, 2016

The nerve agent sarin causes a deadly overstimulation of the nervous system that can be stopped if treated with an antidote within minutes of poisoning. Today, a ground-breaking study has been published in PNAS, which in detail describes how such a drug works. Researchers at the Swedish Defence Research Agency, Umeå University and in Germany are behind the study.

Sarin is a colourless, odourless liquid fatal even at very low concentrations. Serious sarin poisoning causes visual disturbance, vomiting, breathing difficulties and, finally, death.

"Nerve agents are dreadful weapons, and our hope is for these results to lead to improved drugs against them," says Anders Allgardsson, Biochemist at the Swedish Defence Research Agency (FOI).

Nerve agents destroy the function of a very important protein in the nervous system called acetylcholinesterase. As long as the nerve agent is bound to the protein, the breakdown of an important signal substance is prevented. The antidote HI-6 removes the nerve agent and restores the function of the nervous system. Drugs against nerve agent poisoning have been used for a long time, still it has been unclear how they actually work.

After years of hard work, chemists from FOI and Umeå University are now presenting a three-dimensional structure that depicts the HI-6 moments before the bond between the nerve agent and the protein is broken. The structure gives a high-resolution image that, in detail, describes the individual positions of atoms and provides an understanding of how the bond breaks.

The scientific breakthrough was enabled by combining three-dimensional structural depictions with advanced calculations and biochemical experiments.

"With the help of X-ray crystallography, we could see weak traces of the signal we were looking for. As the signal was weak, we decided to integrate the data with quantum chemical methods. After demanding calculations on the supercomputer at the High Performance Computing Center North (HPC2N) at Umeå University, we finally succeeded," says Anna Linusson, Professor at the Department of Chemistry at Umeå University.

The calculations supported the theory that the weak signal in the X-ray crystallography data actually came from HI-6 and sarin. Important knowledge also fell into place after experiments where the system was disturbed by mutating the protein or by introducing isotopes.

"After seven years of work using many different techniques, we have finally been able to bring this to a successful close and can show a uniform picture of how HI-6 approaches sarin. It opens up for new opportunities in finding antidotes to sarin and other nerve agents by structure-based molecular design," says Anders Allgardsson.
-end-
The study is a collaboration between Umeå University, the Swedish Defence Research Agency and the German Bundeswehr Institute of Pharmacology and Toxicology. The results were published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Umea University

Related Nervous System Articles:

Rare cells are 'window into the gut' for the nervous system
Specialized cells in the gut sense potentially noxious chemicals and trigger electrical impulses in nearby nerve fibers, according to a new study led by UC San Francisco scientists.
Study overturns seminal research about the developing nervous system
New research by scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA overturns a long-standing paradigm about how axons grow during embryonic development.
Sympathetic nervous system is critical in regulating energy expenditure and thermogenesis
New study suggests that your brain, not your white blood cells, keeps you warm.
As fins evolve to help fish swim, so does the nervous system
The sensory system in fish fins evolves in parallel to fin shape and mechanics, and is specifically tuned to work with the fish's swimming behavior, according to new research from the University of Chicago.
Antibodies as 'messengers' in the nervous system
Antibodies are able to activate human nerve cells within milliseconds and hence modify their function -- that is the surprising conclusion of a study carried out at Human Biology at the Technical University of Munich (TUM).
Bioimaging: A clear view of the nervous system
A new and versatile imaging technique enables researchers to trace the trajectories of whole nerve cells and provides extensive insights into the structure of neuronal networks.
In the gut, nervous cells are the 'eyes and ears' of the immune system
A team of scientists in Portugal has discovered, in the mouse gut, a novel process that protects the bowel's lining against inflammation and microbial aggressions -- and fights them when they arise.
Biologists discover new strategy to treat central nervous system injury
Neurobiologists at UC San Diego have discovered how signals that orchestrate the construction of the nervous system also influence recovery after traumatic injury.
Delivery strategies of chemotherapy to the central nervous system
The blood-brain barrier and the blood-tumor barrier remain great obstacles to the drug delivery to brain tumors.
520-million-year-old fossilized nervous system is most detailed example yet found
A 520-million-year-old fossilized nervous system -- so well-preserved that individually fossilized nerves are visible -- is the most complete and best example yet found, and could help unravel how the nervous system evolved in early animals.

Related Nervous System Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...