Scientists developing nerve agent fighting drugs

Scientists at Ohio State University are developing new drugs designed to regenerate a critical enzyme in the human body that is altered after exposure to chemical warfare agents.

Christopher Hadad, a chemistry professor at OSU, is utilizing the resources of the Ohio Supercomputer Center to develop a more effective antidote to organophosphorus nerve agents, according to

"This project is a combination of synthetic and computational organic chemistry conducted through OSC at Ohio State, and biochemical studies conducted by colleagues at the U.S. Army Medical Research Institute of Chemical Defense at Aberdeen Proving Ground in Maryland," Hadad said, according to

OP nerve agents stop an enzyme called acetylcholinesterase from turning off messages being delivered by a neurotransmitter called acetylcholine that is capable of activating various muscles, glands and organs throughout the body.

After being exposed to OP agents, acetylcholinesterase alters its structure through an “aging” process, and is left unable to perform its normal functions. Without an effective antidote, neurosynaptic communication continues ceaselessly, causing uncontrolled secretions from the mouth, eyes and nose, as well as severe muscle spasms that, if left without treatment, cause death.

The focus of a number of studies has been on the creation of antidotes that block the activity of the nerve agent by introducing oxime compounds. These compounds adhere to a phosphorus atom of the nerve agent after it has bound to acetylcholinesterase, and then split it away from the enzyme, allowing the acetylcholinesterase to engage with receptors and relax the tissues.

In some cases, however, the combined nerve agent and acetylcholinesterase molecule are left unreceptive to oxime compounds through the “aging” process, reports.

Hadad’s study focuses on the identification of compounds that limit the process and allow treatment with oximes to provide total recovery for those exposed. The project is investigating OP agents such as Tabun, VX, VR, sarin and Soman, all of which adopt similar molecular structures when aging.

Throughout the project, Hadad has been using computational studies to guide him through each objective, as well as to understand the observed results of each experiment.

"Dr. Hadad's work on this project has made use of a range of the tools of electronic structure theory, molecular docking, molecular dynamics and hybrid quantum mechanical/molecular mechanical methods," Ashok Krishnamurthy, the interim co-executive director of OSC, said, reports.