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

2021 ◽  
Vol 22 (15) ◽  
pp. 8152
Author(s):  
Pauline Jacquet ◽  
Benjamin Rémy ◽  
Rowdy P. T. Bross ◽  
Marco van Grol ◽  
Floriane Gaucher ◽  
...  
Keyword(s):  
Neuromuscular Junctions ◽  
Wide Spectrum ◽  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Chemical Warfare ◽  
Toxic Agents ◽  
Warfare Agents ◽  
High Concentrations ◽  
Type V ◽  
Medical Countermeasures

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 minutes. 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.

scholarly journals Detection Papers with Chromogenic Chemosensors for Direct Visual Detection and Distinction of Liquid Chemical Warfare Agents

Chemosensors ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 30 ◽  
Author(s):  
Vladimír Pitschmann ◽  
Lukáš Matějovský ◽  
Kamila Lunerová ◽  
Michal Dymák ◽  
Martin Urban ◽  
...  
Keyword(s):  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Chemical Warfare ◽  
Bromocresol Green ◽  
Ph Indicator ◽  
Nitrogen Mustards ◽  
Experimental Development ◽  
Influence Of Water ◽  
Warfare Agents ◽  
Hydrophobic Treatment

This work provides a summary of our results in the area of the experimental development of detection paper for the detection of liquid phase chemical warfare agents (drops, aerosol), the presence of which is demonstrated by the development of characteristic coloring visible to the naked eye. The basis of the detection paper is a cellulose carrier saturated with the dithienobenzotropone monomer (RM1a)–chromogenic chemosensor sensitive to nerve agents of the G type, blister agent lewisite, or choking agent diphosgene. We achieve a higher coloring brilliance and the limit certain interferences by using this chemosensor in the mix of the o-phenylendiamine-pyronine (PY-OPD). We prove that the addition of the Bromocresol Green pH indicator even enables detection of nerve agents of the V type, or, nitrogen mustards, while keeping a high stability of the detection paper and its functions for other chemical warfare agents. We resolve the resistance against the undesirable influence of water by providing a hydrophobic treatment of the carrier surface.

scholarly journals Enzymatic Degradation of Organophosphorus Pesticides and Nerve Agents by EC: 3.1.8.2

Catalysts ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1365
Author(s):  
Marek Matula ◽  
Tomas Kucera ◽  
Ondrej Soukup ◽  
Jaroslav Pejchal
Keyword(s):  
Catalytic Activity ◽  
Organophosphorus Compounds ◽  
Organophosphorus Pesticides ◽  
Chemical Warfare Agents ◽  
Enzyme Commission Number ◽  
Nerve Agents ◽  
Organophosphorus Acid Anhydrolase ◽  
Warfare Agents ◽  
Heavy Burden ◽  
Medical Countermeasures

The organophosphorus substances, including pesticides and nerve agents (NAs), represent highly toxic compounds. Standard decontamination procedures place a heavy burden on the environment. Given their continued utilization or existence, considerable efforts are being made to develop environmentally friendly methods of decontamination and medical countermeasures against their intoxication. Enzymes can offer both environmental and medical applications. One of the most promising enzymes cleaving organophosphorus compounds is the enzyme with enzyme commission number (EC): 3.1.8.2, called diisopropyl fluorophosphatase (DFPase) or organophosphorus acid anhydrolase from Loligo Vulgaris or Alteromonas sp. JD6.5, respectively. Structure, mechanisms of action and substrate profiles are described for both enzymes. Wild-type (WT) enzymes have a catalytic activity against organophosphorus compounds, including G-type nerve agents. Their stereochemical preference aims their activity towards less toxic enantiomers of the chiral phosphorus center found in most chemical warfare agents. Site-direct mutagenesis has systematically improved the active site of the enzyme. These efforts have resulted in the improvement of catalytic activity and have led to the identification of variants that are more effective at detoxifying both G-type and V-type nerve agents. Some of these variants have become part of commercially available decontamination mixtures.

Some Possibilities to Study New Prophylactics against Nerve Agents

2019 ◽  
Vol 19 (12) ◽  
pp. 970-979 ◽  
Author(s):  
J. Bajgar ◽  
J. Kassa ◽  
T. Kucera ◽  
K. Musilek ◽  
D. Jun ◽  
...  
Keyword(s):  
Cholinesterase Inhibitors ◽  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Chemical Warfare ◽  
Huperzine A ◽  
Acetylcholinesterase Inhibition ◽  
Effective Prophylaxis ◽  
Warfare Agents

Nerve agents belong to the most dangerous chemical warfare agents and can be/were misused by terrorists. Effective prophylaxis and treatment is necessary to diminish their effect. General principles of prophylaxis are summarized (protection against acetylcholinesterase inhibition, detoxification, treatment “in advance” and use of different drugs). They are based on the knowledge of mechanism of action of nerve agents. Among different examinations, it is necessary to test prophylactic effectivity in vivo and compare the results with protection in vitro. Chemical and biological approaches to the development of new prophylactics would be applied simultaneously during this research. Though the number of possible prophylactics is relatively high, the only four drugs were introduced into military medical practice. At present, pyridostigmine seems to be common prophylactic antidote; prophylactics panpal (tablets with pyridostigmine, trihexyphenidyl and benactyzine), transant (transdermal patch containing HI-6) are other means introduced into different armies as prophylactics. Scavenger commercionally available is Protexia®. Future development will be focused on scavengers, and on other drugs either reversible cholinesterase inhibitors (e.g., huperzine A, gallantamine, physostigmine, acridine derivatives) or other compounds.

Future Considerations for the Medical Management of Nerve-Agent Intoxication

2003 ◽  
Vol 18 (3) ◽  
pp. 208-216 ◽  
Author(s):  
Pål Aas
Keyword(s):  
Chemical Warfare Agents ◽  
Nerve Agents ◽  
Nerve Agent ◽  
Chemical Warfare ◽  
Weapons Of Mass Destruction ◽  
Terrorist Attacks ◽  
International Conflicts ◽  
Mass Destruction ◽  
The World ◽  
Warfare Agents

AbstractThe use of chemical warfare agents against civilians and unprotected troops in international conflicts or by terrorists against civilians is considered to be a real threat, particularly following the terrorist attacks on 11 September 2001 against the World Trade Center in New York and against the Pentagon in Washington, DC. Over the past 10 years, terrorists have been planning to use or have used chemical warfare agents on several occasions around the world, and the attacks in 2001 illustrate their willingness to use any means of warfare to cause death and destruction among civilians. In spite of new international treaties with strong verification measures and with an aim to prohibit and prevent the use of weapons of mass destruction, nevertheless, some countries and terrorist groups have been able to develop, produce, and use such weapons, particularly nerve agents, in domestic terrorist attacks or during warfare in international conflicts. This article reviews current medical therapy for nerve-agent intoxication and discusses possible future improvement of medical therapies.Present medical counter-measures against nerve agents are not sufficiently effective particularly in protecting the brain. Therefore, new and more effective countermeasures must be developed to enable better medical treatment of civilians and military personnel following exposure to nerve agents. Therefore, it is important with an enhanced effort by all countries, to improve and increase research in medical countermeasures, in the development of protective equipment, and in carrying out regular training of medical and emergency personnel as well as of military nuclear, biological, or chemical (NBC) units. Only then will nations be able to reduce the risk from and prevent the use of such weapons of mass destruction (WMD).

scholarly journals Mineralization of Paraoxon and Its Use as a Sole C and P Source by a Rationally Designed Catabolic Pathway in Pseudomonas putida

2006 ◽  
Vol 72 (10) ◽  
pp. 6699-6706 ◽  
Author(s):  
Matthew de la Peña Mattozzi ◽  
Sundiep K. Tehara ◽  
Thomas Hong ◽  
Jay D. Keasling
Keyword(s):  
Pseudomonas Putida ◽  
Cholinesterase Inhibitors ◽  
Chemical Warfare Agents ◽  
Chemical Warfare ◽  
Catabolic Pathway ◽  
Warfare Agents ◽  
Phosphorus Source ◽  
High Concentrations ◽  
Synthetic Operon ◽  
Heterologous Pathway

ABSTRACT Organophosphate compounds, which are widely used as pesticides and chemical warfare agents, are cholinesterase inhibitors. These synthetic compounds are resistant to natural degradation and threaten the environment. We constructed a strain of Pseudomonas putida that can efficiently degrade a model organophosphate, paraoxon, and use it as a carbon, energy, and phosphorus source. This strain was engineered with the pnp operon from Pseudomonas sp. strain ENV2030, which encodes enzymes that transform p-nitrophenol into β-ketoadipate, and with a synthetic operon encoding an organophosphate hydrolase (encoded by opd) from Flavobacterium sp. strain ATCC 27551, a phosphodiesterase (encoded by pde) from Delftia acidovorans, and an alkaline phosphatase (encoded by phoA) from Pseudomonas aeruginosa HN854 under control of a constitutive promoter. The engineered strain can efficiently mineralize up to 1 mM (275 mg/liter) paraoxon within 48 h, using paraoxon as the sole carbon and phosphorus source and an inoculum optical density at 600 nm of 0.03. Because the organism can utilize paraoxon as a sole carbon, energy, and phosphorus source and because one of the intermediates in the pathway (p-nitrophenol) is toxic at high concentrations, there is no need for selection pressure to maintain the heterologous pathway.

scholarly journals Chemical weapon in the 20th and 21st centuries. Part 3. Organophosphorus chemical warfare agents used until the year 1970. V-group

2020 ◽  
Vol 68 (4) ◽  
pp. 139-163
Author(s):  
Marcin Kloske ◽  
Zygfryd Witkiewicz
Keyword(s):  
Cold War ◽  
Chemical Warfare Agents ◽  
Chemical Compounds ◽  
Chemical Warfare ◽  
Chemical Weapon ◽  
World War ◽  
Group V ◽  
Toxic Agents ◽  
Warfare Agents ◽  
Post War

The article contains the knowledge about the V-group of organophosphorus chemical warfare agents, named nerve agents, used since their discovery until the year 1970. Group V is the second consecutive collection of CW agents and it contains a number of chemical substances, which were considered up to the year 2018, to be the most toxic chemical compounds included in the arsenal of chemical weapons. Keywords: organophosphorus toxic agents, chemical weapon, II World War, post-war period, Cold War

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