Enzymatic Decontamination of G-Type, V-Type and Novichok Nerve Agents.

Pauline Jacquet,Martijn C De Koning,Benjamin Rémy,Floriane Gaucher,Rowdy P T Bross,David Daudé,Eric Chabrière,Marco Van Grol

doi:10.3390/ijms22158152

Abstract

Organophosphorus nerve agents (OPNAs) are highly toxic compounds inhibiting cholinergic enzymes in the central and autonomic nervous systems and neuromuscular junctions, causing severe intoxications in humans. Medical countermeasures and efficient decontamination solutions are needed to counteract the toxicity of a wide spectrum of harmful OPNAs including G, V and Novichok agents. Here, we describe the use of engineered OPNA-degrading enzymes for the degradation of various toxic agents including insecticides, a series of OPNA surrogates, as well as real chemical warfare agents (cyclosarin, sarin, soman, tabun, VX, A230, A232, A234). We demonstrate that only two enzymes can degrade most of these molecules at high concentrations (25 mM) in less than 5 min. Using surface assays adapted from NATO AEP-65 guidelines, we further show that enzyme-based solutions can decontaminate 97.6% and 99.4% of 10 g∙m−2 of soman- and VX-contaminated surfaces, respectively. Finally, we demonstrate that these enzymes can degrade ethyl-paraoxon down to sub-inhibitory concentrations of acetylcholinesterase, confirming their efficacy from high to micromolar doses.

Highlights

organophosphorus nerve agents (OPNAs) can be divided into three groups: (i) G-agents (G for German) including sarin, cyclosarin, tabun and soman, which are known as non-persistent; (ii) V-agents (V for Venomous, Victory or Viscous, depending on the source) such as VX, which are persistent; and (iii) compounds belonging to the A-series of agents, or Novichok agents
While the use of OPNAs is banned by the Organisation for the Prohibition of Chemical Weapons (OPCW), recent examples show that these agents are still considered in terrorist attacks and asymmetric conflicts, constituting a serious threat for populations
Concentrations of (1a) and (2) remain unchanged after enzyme removal, suggesting that conversion of (1a) to (2) is enzymatically catalysed (Supplementary Figure S17). These results demonstrate that engineered PTE can be active against Novichok agents, a finding that has not previously been reported, to the best of our knowledge, showing that an enzyme-based solution, which is active against the whole spectrum of OPNA, can be obtained

Summary

Introduction

Organophosphorus chemicals (OPs) are highly toxic compounds inhibiting cholinesterase enzymes from the central nervous system and causing severe poisoning in humans [1,2].They have been developed as organophosphorus nerve agents (OPNAs) for military purposes but have been considered for use in agriculture and constitute the first class of insecticides worldwide responsible for severe acute and chronic intoxications [3,4,5,6].OPNAs can be divided into three groups: (i) G-agents (G for German) including sarin, cyclosarin, tabun and soman, which are known as non-persistent; (ii) V-agents (V for Venomous, Victory or Viscous, depending on the source) such as VX, which are persistent; and (iii) compounds belonging to the A-series of agents, or Novichok agents (SupplementaryFigure S1) [5,7]. Organophosphorus chemicals (OPs) are highly toxic compounds inhibiting cholinesterase enzymes from the central nervous system and causing severe poisoning in humans [1,2]. They have been developed as organophosphorus nerve agents (OPNAs) for military purposes but have been considered for use in agriculture and constitute the first class of insecticides worldwide responsible for severe acute and chronic intoxications [3,4,5,6]. Sarin was used in Syria in 2013 [8,9], VX in Malaysia (2017) [10] and, more recently, Novichok agents were used in the UK (2018) and Russia (2020) for poisoning purposes [11,12,13]. The recent events involving Novichok agents have sparked interest in these new compounds, and a number of publications have appeared since their use in

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Conclusion