Computational enzymology for degradation of chemical warfare agents: promising technologies for remediation processes.

Alexandre A De Castro,Teodorico C Ramalho,Daniela R Silva,Tamiris M Assis,Giovanna C Gajo,Flávia V Soares,Silviana Corrêa,Letícia C Assis

doi:10.3934/microbiol.2017.1.108

Abstract

Chemical weapons are a major worldwide problem, since they are inexpensive, easy to produce on a large scale and difficult to detect and control. Among the chemical warfare agents, we can highlight the organophosphorus compounds (OP), which contain the phosphorus element and that have a large number of applications. They affect the central nervous system and can lead to death, so there are a lot of works in order to design new effective antidotes for the intoxication caused by them. The standard treatment includes the use of an anticholinergic combined to a central nervous system depressor and an oxime. Oximes are compounds that reactivate Acetylcholinesterase (AChE), a regulatory enzyme responsible for the transmission of nerve impulses, which is one of the molecular targets most vulnerable to neurotoxic agents. Increasingly, enzymatic treatment becomes a promising alternative; therefore, other enzymes have been studied for the OP degradation function, such as phosphotriesterase (PTE) from bacteria, human serum paraoxonase 1 (HssPON1) and diisopropyl fluorophosphatase (DFPase) that showed significant performances in OP detoxification. The understanding of mechanisms by which enzymes act is of extreme importance for the projection of antidotes for warfare agents, and computational chemistry comes to aid and reduce the time and costs of the process. Molecular Docking, Molecular Dynamics and QM/MM (quantum-mechanics/molecular-mechanics) are techniques used to investigate the molecular interactions between ligands and proteins.

Highlights

Chemical weapons are part of a group of mass destruction weapons that represent a major threat to society
Enzymatic treatment becomes a promising alternative; other enzymes have been studied for the organophosphorus compounds (OP) degradation function, such as phosphotriesterase (PTE) from bacteria, human serum paraoxonase 1 (HssPON1) and diisopropyl fluorophosphatase (DFPase) that showed significant performances in OP detoxification
The use of toxic and warfare nerve agents has been reported since antiquity, and the most recent employ of this kind of weapon took place in Syria, on August 21, 2013, where there was an attack with the neurotoxic agent Sarin (OP derivative), resulting in more than 3,600 victims [6]

Summary

Introduction

Chemical weapons are part of a group of mass destruction weapons that represent a major threat to society They constitute a non-conventional class of low-cost, with difficult detection and control [1]. In this context, organophosphorus compounds (OP) are organic compounds quite used in the fight against pests in agriculture, because they are relatively cheap and present activity on different pests [2,3]. Organophosphorus compounds (OP) are organic compounds quite used in the fight against pests in agriculture, because they are relatively cheap and present activity on different pests [2,3] They are very dangerous because of their neurotoxic effects which can cause serious damage to health public and environment [4,5]. Due to the wide use of these agents, the current concern is to design effective antidotes for the poisoning caused by them [4]

Methods

Results

Conclusion