PoisonPoison: Chasing the Antidote

Published 8 August 2020

While targeted chemical attacks on civilians tend to make headlines, the most common poisoning reports in the United States are from accidental exposure to household chemicals such as insect sprays, cleaning solutions or improperly washed fruit or vegetables. In any case, the remedy is a fast-acting, poison-chasing drug compound, and Oak Ridge National Laboratory says it is on the forefront developing a new generation of life-saving antidotes.

Pick your poison. It can be deadly for good reasons such as protecting crops from harmful insects or fighting parasite infection as medicine — or for evil as a weapon for bioterrorism. Or, in extremely diluted amounts, it can be used to enhance beauty.

While targeted chemical attacks on civilians tend to make headlines, the most common poisoning reports in the United States are from accidental exposure to household chemicals such as insect sprays, cleaning solutions or improperly washed fruit or vegetables. In any case, the remedy is a fast-acting, poison-chasing drug compound, and Oak Ridge National Laboratory is on the forefront developing a new generation of life-saving antidotes.

Simply put, “a poison is something that acutely degrades your health, or your health state,” said Andrey Kovalevsky, a crystallographer and biochemist at ORNL. He is an expert in atomic-level understanding of enzyme function, drug binding and drug resistance. Using neutrons and X-rays, he studies how enzymes work in the body and, depending on the specifics, how to inhibit or reactivate them using small organic molecules.

“Depending on the poison and amount, the effect can be very quick — within seconds — or it can be slow,” he added. The body triggers its own defenses to counteract a poisonous substance; however, it’s usually not enough. Any level of exposure could be deadly, especially if the type of poison is not immediately known to a first responder or medical team attending to an affected patient.

An antidote must act fast — before the poison does irreversible damage — to be effective and save lives.

Mirror the Poison
Kovalevsky is part of a team, led by Zoran Radić of the University of California, San Diego’s Skaggs School of Pharmacy and Pharmaceutical Sciences, developing a new family of antidotes for poisons called organophosphates, which include nerve agents. Radić’s research uniquely targets the root cause of organophosphate poisoning, going beyond just treating the symptoms as with existing remedies.

Their focus is on the complex biochemical mechanisms that control and maintain the body’s nervous system. They start with acetylcholine, or ACh, which is a compound found at the junction of muscles and nerves and also in the brain. ACh functions as a neurotransmitter that maintains normal communication between nerves and muscles. But ACh doesn’t act alone.