Researchers Discover Process to Combat the Effects of Nerve Agents

Researchers Discover Process to Combat the Effects of Nerve Agents

Sarin nerve gas molecule

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Sarin is a colorless, odorless liquid fatal even at very low concentrations. Serious sarin poisoning causes visual disturbance, vomiting, breathing difficulties and, finally, death. The nerve agent causes a deadly overstimulation of the nervous system that can only be stopped if treated with an antidote within minutes of poisoning. Now, Homeland Security News Wire reports, a ground-breaking study done by Swedish and German researchers has been published in PNAS, which describes in detail how such a drug works.

Nerve agents destroy the function of a very important protein in the nervous system called acetylcholinesterase. The antidote HI-6 removes the nerve agent chained to the protein and which prevents it from functioning 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.

“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 Defense Research Agency (FOI), who took part in the research.

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. The study describes a model which shows how sarin and HI-6 are positioned in the protein acetylcholinesterase just before HI-6 removes sarin and restores the function of the protein. The model was developed by a combination of X-ray crystallography and quantum chemical calculations. Sarin in magenta, HI6 in green, oxygen in red, phosphorus in orange, and nitrogen in blue.

“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 at Umeå University, we finally succeeded,” says Anna Linusson, Professor at the Department of Chemistry at Umeå University.