Chemical warfare: Perspectives on reactivating the enzyme acetylcholinesterase inhibited by organophosphates

Abstract

Recent attacks on Syria using the nerve agent sarin warned once again the world and the scientists on the use of chemical weapons. It is known that nerve agents are potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of the neurotransmitter acetylcholine and, thus, transmitting of nerve impulses. The process of AChE inhibition by organophosphate (OP) can be reversed by a nucleophile, responsible for dephosphorylation of the residue Ser203 in the active site of the enzyme. In this sense, oximes exhibit this characteristic and are able to remove the neurotoxic and reactivate the enzyme. Here, we review experimental and theoretical results involving docking and quantum mechanical-molecular mechanics hybrid methods (QM/MM), using Molegro® and Spartan® softwares to analyze the interaction of different OPs and oximes with AChE and to evaluate kinetic constants of reactivation.