Novichok
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Novichok () is a family of nerve agents, some of which are
binary chemical weapon __NOTOC__ Binary chemical weapons or munitions are chemical weapons which contain the toxic agent in its active state as chemical precursors that are significantly less toxic than the agent. This improves the safety of storing, transporting, and ...
s. The agents were developed at the
GosNIIOKhT The State Research Institute of Organic Chemistry and Technology () (GosNIIOKhT) is a Russian research institute engaged in the development of chemical technologies for use in the national economy and the production of relevant goods and prod ...
state chemical research institute by the
Soviet Union The Union of Soviet Socialist Republics. (USSR), commonly known as the Soviet Union, was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 until Dissolution of the Soviet ...
and Russia between 1971 and 1993. Some Novichok agents are
solids Solid is a state of matter where molecules are closely packed and can not slide past each other. Solids resist compression, expansion, or external forces that would alter its shape, with the degree to which they are resisted dependent upon the ...
at
standard temperature and pressure Standard temperature and pressure (STP) or standard conditions for temperature and pressure are various standard sets of conditions for experimental measurements used to allow comparisons to be made between different sets of data. The most used ...
, while others are
liquids Liquid is a state of matter with a definite volume but no fixed shape. Liquids adapt to the shape of their container and are nearly incompressible, maintaining their volume even under pressure. The density of a liquid is usually close to th ...
. Dispersal of solid form agents is thought possible if in ultrafine powder state. Russian scientists who developed the nerve agents claim they are the deadliest ever made, with some variants possibly five to eight times more potent than VX, and others up to ten times more potent than soman.
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has also been associated with the production of such chemical agents. In the twenty-first century, Novichok agents came to public attention after they were used to poison opponents of the Russian government, including the Skripals and two others in Amesbury, UK (2018), as well as
Alexei Navalny Alexei Anatolyevich Navalny (, ; 4 June 197616 February 2024) was a Russian Opposition to Vladimir Putin in Russia, opposition leader, anti-corruption in Russia, corruption activist and political prisoner. He founded the Anti-Corruption Found ...
(2020), but Russian civil poisonings with this substance have been known since at least 1995. In November 2019, the
Organisation for the Prohibition of Chemical Weapons The Organisation for the Prohibition of Chemical Weapons (OPCW; French: ''Organisation pour l'interdiction des armes chimiques'', OIAC) is an intergovernmental organisation and the implementing body for the Chemical Weapons Convention (CWC), ...
(OPCW), which is the executive body for the
Chemical Weapons Convention The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
(CWC), added the Novichok agents to "list of controlled substances" of the CWC "in one of the first major changes to the treaty since it was agreed in the 1990s" in response to the 2018 poisonings in the UK.


Design objectives

Novichok agents were designed to achieve four objectives: * to be undetectable using standard 1970s and 1980s
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chemical detection equipment; * to defeat NATO chemical protective gear; * to be safer to handle; and * to circumvent the
Chemical Weapons Convention The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
list of controlled precursors, classes of chemical and physical form. Some of these agents are binary weapons, in which precursors for the nerve agents are mixed in a munition to produce the agent just prior to its use. The precursors are generally significantly less hazardous than the agents themselves, so this technique makes handling and transporting the munitions a great deal simpler. Additionally, precursors to the agents are usually much easier to stabilise than the agents themselves, so this technique also makes it possible to increase the
shelf life Shelf life is the length of time that a commodity may be stored without becoming unfit for use, consumption, or sale. In other words, it might refer to whether a commodity should no longer be on a pantry shelf (unfit for use), or no longer on a s ...
of the agents. This has the disadvantage that careless preparation may produce a non-optimal agent. During the 1980s and 1990s, binary versions of several Soviet agents were developed and are designated as "Novichok" agents.


History and disclosure

Novichok agents were designed as part of a Soviet program codenamed Foliant. Five Novichok variants are believed to have been adapted for military use. The most versatile is A-232 (Novichok-5). Novichok agents have never been used on the battlefield. The UK government determined that a Novichok agent was used in the
poisoning of Sergei and Yulia Skripal The poisoning of Sergei and Yulia Skripal, also known as the Salisbury poisoning, was a botched assassination attempt to poison Sergei Skripal, a former Russian military officer and double agent for the British intelligence agencies in the cit ...
in Salisbury, Wiltshire, England in March 2018. It was unanimously confirmed by four laboratories around the world, according to the OPCW. Novichok was also involved in the poisoning of a British couple in Amesbury, Wiltshire, four months later, believed to have been caused by residual nerve agent discarded after the Salisbury attack. The attacks led to the death of one person, left three others in a critical condition from which they recovered, and briefly hospitalised a police officer. The Russian government denies producing or researching agents "under the title Novichok". In September 2020, the
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government said that opposition figure and anti-corruption activist
Alexei Navalny Alexei Anatolyevich Navalny (, ; 4 June 197616 February 2024) was a Russian Opposition to Vladimir Putin in Russia, opposition leader, anti-corruption in Russia, corruption activist and political prisoner. He founded the Anti-Corruption Found ...
, who was evacuated from
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to
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for treatment in late August after becoming ill during his flight, was poisoned by a Novichok agent. Novichok has been known to most Western intelligence services since the 1990s, and in 2016 Iranian chemists working at a university in Tehran synthesised five of the seven Novichok agents for analysis and produced detailed
mass spectroscopy Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...
data which was added to the OPCW's Central Analytical Database. Previously, there had been no detailed descriptions of their spectral properties in peer-reviewed general scientific literature. A small amount of agent A-230 was also claimed to have been synthesised in the Czech Republic in 2017 for the purpose of obtaining analytical data to help defend against these novel toxic compounds. The Soviet Union and Russia reportedly developed extremely potent fourth-generation chemical weapons from the 1970s until the early 1990s, according to a publication by two chemists, Lev Fyodorov and Vil Mirzayanov, in '' Moskovskiye Novosti'' weekly in 1992. The publication appeared just on the eve of Russia's signing of the
Chemical Weapons Convention The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
. According to Mirzayanov, the Russian Military Chemical Complex (MCC) was using defence conversion money received from the West for development of a chemical warfare facility. Mirzayanov made his disclosure out of environmental concerns. He was the head of a counter-intelligence department and performed measurements outside the chemical weapons facilities to make sure that foreign spies could not detect any traces of production. To his horror, the levels of deadly substances were eighty times greater than the maximum safe concentration. The Prosecutor-General of Russia effectively admitted the existence of Novichok agents when he brought a
treason Treason is the crime of attacking a state (polity), state authority to which one owes allegiance. This typically includes acts such as participating in a war against one's native country, attempting to Coup d'état, overthrow its government, spy ...
case against Mirzayanov. According to expert witness testimonies that three scientists prepared for the
KGB The Committee for State Security (, ), abbreviated as KGB (, ; ) was the main security agency of the Soviet Union from 1954 to 1991. It was the direct successor of preceding Soviet secret police agencies including the Cheka, Joint State Polit ...
, Novichok and other related chemical agents had indeed been produced and therefore Mirzayanov's disclosure represented
high treason Treason is the crime of attacking a state authority to which one owes allegiance. This typically includes acts such as participating in a war against one's native country, attempting to overthrow its government, spying on its military, its d ...
. Mirzayanov was arrested on 22 October 1992 and sent to Lefortovo prison for divulging state secrets. He was released later because "not one of the formulas or names of poisonous substances in the ''Moscow News'' article was new to the Soviet press, nor were locations ... of testing sites revealed." According to Yevgenia Albats, "the real state secret revealed by Fyodorov and Mirzayanov was that generals had lied—and were still lying—to both the international community and their fellow citizens." Mirzayanov now lives in the U.S. Further disclosures followed when Vladimir Uglev, one of Russia's leading binary weapons scientists, revealed the existence of A-232/Novichok-5 in an interview with the magazine '' Novoye Vremya'' in early 1994. In his 1998 interview with David E. Hoffman for ''
The Washington Post ''The Washington Post'', locally known as ''The'' ''Post'' and, informally, ''WaPo'' or ''WP'', is an American daily newspaper published in Washington, D.C., the national capital. It is the most widely circulated newspaper in the Washington m ...
'' the chemist claimed that he helped invent the A-232 agent, that it was more frostproof, and confirmed that a binary version has been developed from it. Uglev revealed more details in 2018, following the poisoning of the Skripals, stating that "several hundred" compounds were synthesised during the Foliant research but only four agents were weaponised (presumably the Novichok-5, −7, −8 and −9 mentioned by other sources): the first three were liquids and only the last, which was not developed until 1980, could be made into a powder. Unlike the interview twenty years earlier, he denied any binary agents were developed successfully, at least up until his involvement in the research ceased in 1994. In the 1990s, the German
Federal Intelligence Service The Federal Intelligence Service (, ; BND) is the foreign intelligence agency of Germany, directly subordinate to the Chancellor's Office. The BND headquarters is located in central Berlin. The BND has 300 locations in Germany and foreign cou ...
(BND) obtained a sample of one Novichok agent from a Russian scientist, and the sample was analysed in Sweden, according to a 2018 ''
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'' report. The chemical formula was given to Western
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countries, who synthesized it, then used small amounts to test protective equipment, detection of it, and antidotes to it. Novichok was referred to in a patent filed in 2008 for an organophosphorus poisoning treatment. The
University of Maryland, Baltimore The University of Maryland, Baltimore (UMB) is a public university in Baltimore, Maryland, United States. Founded in 1807, it is the second oldest college in Maryland and comprises some of the oldest professional schools of dentistry, law, me ...
research was funded in part by the
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. Professor Leonid Rink, who said he had participated in the creation of Novichok agents, confirmed that the structures leaked by Mirzayanov were the correct ones. Rink was himself convicted in Russia for illegally selling a Novichok agent used in 1995 to assassinate a banker, Ivan Kivelidi, and his secretary. David Wise, in his book ''Cassidy's Run'', implies that the Soviet program may have been the unintended result of misleading information, involving a discontinued American program to develop a nerve agent code named " GJ", that was fed by a double agent to the Soviets as part of Operation Shocker.


Development and test sites

Stephanie Fitzpatrick, an American geopolitical consultant, has claimed that the Chemical Research Institute in Nukus, Soviet Uzbekistan, produced Novichok agents, and ''
The New York Times ''The New York Times'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of ...
'' has reported that U.S. officials said the site was the major research and testing site for Novichok agents. Small, experimental batches of the weapons may have been tested on the nearby Ustyurt Plateau. Fitzpatrick also writes that the agents may have been tested in a research centre in Krasnoarmeysk near Moscow. Precursor chemicals were made at the Pavlodar Chemical Plant in Soviet Kazakhstan, which was also thought to be the intended Novichok weapons production site, until its still-under-construction chemical warfare agent production building was demolished in 1987 in view of the forthcoming 1990 Chemical Weapons Accord and the
Chemical Weapons Convention The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
. Since its independence in 1991,
Uzbekistan , image_flag = Flag of Uzbekistan.svg , image_coat = Emblem of Uzbekistan.svg , symbol_type = Emblem of Uzbekistan, Emblem , national_anthem = "State Anthem of Uzbekistan, State Anthem of the Republ ...
has been working with the government of the United States to dismantle and decontaminate the sites where the Novichok agents and other chemical weapons were tested and developed. Between 1999 and 2002 the
United States Department of Defense The United States Department of Defense (DoD, USDOD, or DOD) is an United States federal executive departments, executive department of the federal government of the United States, U.S. federal government charged with coordinating and superv ...
dismantled the major research and testing site for Novichok at the Chemical Research Institute in Nukus, under a $6 million Cooperative Threat Reduction program. Hamish de Bretton-Gordon, a British chemical weapons expert and former commanding officer of the UK's Joint Chemical, Biological, Radiation and Nuclear Regiment and its NATO equivalent, "dismissed" suggestions that Novichok agents could be found in other places in the former Soviet Union such as Uzbekistan and has asserted that Novichok agents were produced only at Shikhany in
Saratov Oblast Saratov Oblast is a federal subjects of Russia, federal subject of Russia (an oblast), located in the Volga Federal District. Its administrative center is the types of inhabited localities in Russia, city of Saratov. As of the 2021 Russian cens ...
, Russia. Mirzayanov also says that it was at Shikhany, in 1973, that scientist Pyotr Petrovich Kirpichev first produced Novichok agents; Vladimir Uglev joined him on the project in 1975. According to Mirzayanov, while production took place in Shikhany, the weapon was ''tested'' at Nukus between 1986 and 1989. Following the poisoning of the Skripals, former head of the GosNIIOKhT security department Nikolay Volodin confirmed in an interview to ''
Novaya Gazeta ''Novaya Gazeta'' (, ) is an independent Russian newspaper. It is known for its critical and investigative coverage of Russian political and social affairs, the Chechen wars, corruption among the ruling elite, and increasing authoritarianism i ...
'' that there have been tests at Nukus, and said that dogs were used. In May 2018, the ''
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'' reported that "Germany's foreign intelligence service secured a sample of the Soviet-developed nerve agent Novichok in the 1990s and passed on its knowledge to partners including Britain and the US, according to German media reports." The sample was analysed in Sweden. Small amounts of the Novichok nerve agent were subsequently produced in some
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countries for test purposes.


Description of Novichok agents

Mirzayanov provided the first description of these agents. Dispersed in an ultra-fine
powder A powder is a dry solid composed of many very fine particles that may flow freely when shaken or tilted. Powders are a special sub-class of granular materials, although the terms ''powder'' and ''granular'' are sometimes used to distinguish se ...
instead of a gas or a vapour, they have unique qualities. A binary agent was then created that would mimic the same properties but would either be manufactured using materials which are not controlled substances under the CWC, or be undetectable by treaty regime inspections. The most potent compounds from this family, Novichok-5 and Novichok-7, are supposedly around five to eight times more potent than VX. The "Novichok" designation refers to the binary form of the agent, with the final compound being referred to by its code number (e.g. A-232). The first Novichok series compound was in fact the binary form of a known V-series nerve agent, VR, while the later Novichok agents are the binary forms of compounds such as A-232 and A-234. According to a classified (secret) report by the US Army National Ground Intelligence Center in '' Military Intelligence Digest'' dated 24 January 1997, agent designated A-232 and its ethyl analogue A-234 developed under the Foliant programme "are as toxic as VX, as resistant to treatment as soman, and more difficult to detect and easier to manufacture than VX". The binary versions of the agents reportedly use
acetonitrile Acetonitrile, often abbreviated MeCN (methyl cyanide), is the chemical compound with the formula and structure . This colourless liquid is the simplest organic nitrile (hydrogen cyanide is a simpler nitrile, but the cyanide anion is not class ...
and an organic phosphate "that can be disguised as a pesticide precursor." The agent A-234 is also supposedly around five to eight times more potent than VX. The median lethal dose for inhaled A-234 has been estimated as 7 mg/m3 for two minute exposure (minute volume of 15 L, slight activity). The median lethal dose for inhaled A-230, likely the most toxic liquid Novichok, has been estimated as between 1.9 and 3 mg/m3 for two minute exposure. Thus the median lethal dose for inhaled A-234 is 0.2 mg (5000 lethal doses in a gram) and is below 0.1 mg for A-230 (10 000 lethal doses in a gram). The agents are reportedly capable of being delivered as a liquid, aerosol or gas via a variety of systems, including artillery shells, bombs, missiles and spraying devices.


Controversy over formulation

Mirzayanov gives somewhat different structures for Novichok agents in his autobiography than those which have been identified by Western experts. The Western formulations suffered from imperfect information, as can be seen in Fig. 1 of Chai ''et al'' in which Mirzayanov describes a family of compounds whereas Western scientists instantiate a particular salt. Mirzyanov makes clear that a large number of compounds were made, and many of the less potent derivatives were reported in the open literature as new organophosphate insecticides, so that the secret chemical weapons program could be disguised as legitimate pesticide research.


Chemistry

According to chemical weapons expert
Jonathan Tucker Jonathan Moss Tucker (born May 31, 1982) is an American actor. He is known for his roles in the films ''The Virgin Suicides'' (1999), ''The Texas Chainsaw Massacre'' (2003), ''Hostage'' (2005), '' In the Valley of Elah'' (2007), '' The Ruins'' (2 ...
, the first binary formulation developed under the Foliant programme was used to make Substance 33 ( VR), very similar to the more widely known VX, differing only in the alkyl substituents on its nitrogen and oxygen atoms. "This weapon was given the code name Novichok." A wide range of potential structures have been reported. These all feature the classical organophosphorus core (sometimes with the P=O replaced with P=S or P=Se), which is most commonly depicted as being a phosphoramidate or
phosphonate In organic chemistry, phosphonates or phosphonic acids are organophosphorus compounds containing Functional group, groups, where R is an organic group (alkyl, aryl). If R is hydrogen then the compound is a Phosphite_ester#Chemistry_of_HP(O)(OR ...
, usually fluorinated (cf. monofluorophosphate). The organic groups are subject to more variety; however, a common substituent is
phosgene oxime Phosgene oxime, or CX, is an organic compound with the formula . It is a potent chemical weapon, specifically a nettle agent. The compound itself is a colorless solid, but impure samples are often yellowish liquids. It has a strong, disagreeable ...
or analogues thereof. This is a potent chemical weapon in its own right, specifically as a
nettle agent Nettle agents (named after stinging nettles) or urticants are a variety of chemical warfare agents that produce corrosive skin and tissue injury upon contact, resulting in erythema, urticaria, intense itching, and a hive-like rash. Most nettle ...
, and would be expected to increase the harm done by the Novichok agent. Many claimed structures from this group also contain cross-linking agent motifs which may covalently bind to the
acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...
enzyme's active site in several places, perhaps explaining the rapid denaturing of the enzyme that is claimed to be characteristic of the Novichok agents. Zoran Radić, a chemist at the University of California, San Diego, performed an ''in silico'' docking study with Mirzayanov's version of the A-232 structure against the active site of the acetylcholinesterase enzyme. The model predicted a tight fit with high binding affinity and formation of a
covalent bond A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...
to a
serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...
residue in the active site, with a similar binding mode to established nerve agents such as sarin and soman.


Detection

A procedure of retrospective detection of Novichok type poisons in victim's tissues was proposed in 2021-2.Daan Noort,* Alex Fidder, Debora van der Riet-van Oeveren, Ruud Busker, and Marcel J. van der Schans. Verification of Exposure to Novichok Nerve Agents Utilizing a Semitargeted Human Butyrylcholinesterase Nonapeptide Assay. ''Chem. Res. Toxicol.'' 2021, 34, 1926−1932 This method is a modification of the procedure that was developed earlier for identification of sarin poisoning.Fidder, A., Noort, D., Hulst, A. G., De Ruiter, R., Van der Schans, M. J., Benschop, H. P., and Langenberg, J. P. (2002) Retrospective detection of exposure to organophosphorus anti-cholinesterases: mass spectrometric analysis of phosphylated human butyrylcholinesterase. ''Chem. Res. Toxicol.'' 15, 582−590. This method capitalizes on the fact that poisoning by organic phosphonates occurs via phosphonylation of the hydroxy group of serine in the active site of cholinesterases, and that severe poisoning occurs when a major part of these enzymes are inactivated. The concentration of butyryl cholinesterase (HuBuChE) in human plasma is normally about 80 nM. That makes it a good source of adducts that can be subjected to analysis. The procedure consists of three steps (see the Figure A). First, HuBuChE is obtained from the victim's plasma. Second, the enzyme is subjected to pepsin proteolysis. Third, the peptide mixture obtained is subjected to LC-MSMS analysis. If no poisoning took place, the peptide mixture contains a non-modified nonapeptide FGESAGAAS. However, cholinesterases are inactivated due to a chemical reaction with Novichok type nerve agent, the modified nonapeptide is be detected, and its exact (high resolution) mass (along with the mass of the secondary ion produced during collision induced dissociation) allows unambiguous identification of the fact of poisoning and the exact structure of the poison. Thus, the example at Figure A shows the masses of the primary and secondary ions obtained from the plasma of the victim poisoned by A-230. If a victim is poisoned by other Novichok type agents, the masses are different. This method allows identification of poisons at a few parts per billion, but that may be insufficient for reliable detection of the isotopic signature of the adducts, and therefore an unambiguous identification of the geographic origin of the poison.


Lifetime

According to Vladimir Uglev, who headed a group that worked on the development of the Novichok agents, at least one liquid form of Novichok is very stable with a slow evaporation rate and can remain potent for possibly up to 50 years. Insufficient research has been conducted to fully understand its persistence in various situations in the environment.


Effects and countermeasures

As nerve agents, the Novichok agents belong to the class of
organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...
acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level an ...
s. These chemical compounds inhibit the enzyme
acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...
, preventing the normal breakdown of the
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...
acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
. Acetylcholine concentrations then increase at neuromuscular junctions to cause involuntary contraction of all skeletal muscles (
cholinergic crisis A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine, as a result of the inactivity of the acetylcholinesterase enzyme, which normally breaks down acetylcholine. Signs and symptoms As a resul ...
). This then leads to respiratory and cardiac arrest (as the victim's heart and diaphragm muscles no longer function normally) and finally death from heart failure or suffocation as copious fluid secretions fill the victim's lungs. As can be seen with other organophosphate poisonings, Novichok agents may cause lasting nerve damage, resulting in permanent disablement of victims, according to Russian scientists. Their effect on humans was demonstrated by the accidental exposure of Andrei Zheleznyakov, one of the scientists involved in their development, to the residue of an unspecified Novichok agent while working in a Moscow laboratory in May 1987. He was critically injured and took ten days to recover consciousness after the incident. He lost the ability to walk and was treated at a secret clinic in Leningrad for three months afterwards. The agent caused permanent harm, with effects that included "chronic weakness in his arms, a toxic hepatitis that gave rise to cirrhosis of the liver, epilepsy, spells of severe depression, and an inability to read or concentrate that left him totally disabled and unable to work." He never recovered and, after five years of deteriorating health, died in July 1992. The use of a fast-acting peripheral
anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...
drug such as
atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...
can block the receptors where acetylcholine acts to prevent poisoning (as in the treatment for poisoning by other acetylcholinesterase inhibitors). Atropine, however, is difficult to administer safely, because its effective dose for nerve agent poisoning is close to the dose at which patients suffer severe side effects, such as changes in heart rate and thickening of the bronchial secretions, which fill the lungs of someone suffering nerve agent poisoning so that suctioning of these secretions, and other advanced life support techniques, may be necessary in addition to administration of atropine to treat nerve agent poisoning. In the treatment of nerve agent poisoning, atropine is most often administered along with a Hagedorn oxime such as pralidoxime, obidoxime, TMB-4, or HI-6, which reactivates acetylcholinesterase which has been inactivated by
phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...
by an organophosphorus nerve agent and relieves the respiratory muscle paralysis caused by some nerve agents. Pralidoxime is not effective in reactivating acetylcholinesterase inhibited by some older nerve agents such as soman or the Novichok nerve agents, described in the literature as being up to eight times more toxic than the nerve agent VX. The US Army has funded studies of the use of
galantamine Galantamine is a type of acetylcholinesterase inhibitor. It is an alkaloid extracted from the bulbs and flowers of ''Galanthus nivalis'' (common snowdrop), '' Galanthus caucasicus'' (Caucasian snowdrop), '' Galanthus woronowii'' (Voronov's snow ...
along with atropine in the treatment of a number of nerve agents, including soman and the Novichok agents. An unexpected synergistic interaction was seen to occur between galantamine (given between five hours before to thirty minutes after exposure) and atropine in an amount of 6 mg/kg or higher. Increasing the dose of galantamine from 5 to 8 mg/kg decreased the dose of atropine needed to protect experimental animals from the toxicity of soman in dosages 1.5 times the LD50 (lethal dose in half the animals studied). There have been differing claims about the persistence of Novichok and binary precursors in the environment. One view is that it is not affected by normal weather conditions, and may not decompose as quickly as other
organophosphates In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...
. However, Mirzayanov states that Novichok decomposes within four months.


Instances of usage


Poisoning of Ivan Kivelidi and Zara Ismailova

A Novichok agent was used in 1995 to poison Russian banker , who died three days later in a hospital at the age of 46. The poison was believed to have been applied to Kivelidi's office phone in Moscow. His secretary Zara Ismailova also developed symptoms one month later and then died a day later in a hospital at the age of 35. Kivelidi was the head of the Russian Business Round Table, and had close ties to
Viktor Chernomyrdin Viktor Stepanovich Chernomyrdin (, ; 9 April 19383 November 2010) was a Soviet and Russian politician and businessman. He was the Minister of Gas Industry of the Soviet Union (13 February 1985 – 17 July 1989), after which he became first chairm ...
, who was at that time
Prime Minister of Russia The prime minister of the Russian Federation, also domestically stylized as the chairman of the government of the Russian Federation and widely recognized as the prime minister, is the head of government of Russia and the second highest ranking ...
.
Russian opposition Opposition to the government of President Vladimir Putin in Russia, commonly referred to as the Russian opposition, can be divided between the parliamentary opposition parties in the State Duma and the various Non-system opposition, non-systemi ...
–linked historians Yuri Felshtinsky and Vladimir Pribylovsky speculated that the murder became "one of the first in the series of poisonings organised by Russia's security services". The
Russian Ministry of Internal Affairs The Ministry of Internal Affairs of the Russian Federation (MVD; , ''Ministerstvo vnutrennikh del'') is the interior ministry of Russia. The MVD is responsible for law enforcement in Russia through its agencies the Police of Russia, Migratio ...
analysed the substance and announced that it was "a phosphorus-based military-grade nerve agent" "whose formula was strictly classified". According to Nesterov, the administrative head of Shikhany, he did not know of "a single case of such poison being sold illegally" and noted that the poison "is used by professional spies". Vladimir Khutsishvili, a former business partner of Kivelidi's, was subsequently convicted of the killings. According to ''The Independent'', "A closed trial found that his business partner had obtained the substance via intermediaries from an employee of the State Research Institute of Organic Chemistry and Technology (ГосНИИОХТ / GosNIIOKhT), which was involved in the development of Novichok agents. However, Khutsishvili, who claimed that he was innocent, had not been detained at the time of the trial and freely left the country. He was only arrested in 2006 after he returned to Russia, believing that the ten-year old case was closed. Felshtinsky and Pribylovsky claimed that Russia's security services, which had access to the chemical agent, had framed Khutsishvili for the murder, and that the security services had organised the murder on the orders of a senior Russian state official. Boris Kuznetsov, who represented Khutsishvili and believed in his innocence, blames "rogue intelligence officers". Leonid Rink, an employee of GosNIIOKhT, received a one-year suspended sentence for selling Novichok agents to unnamed buyers "of Chechen ethnicity" soon after the poisoning of Kivelidi and Izmailova.


Poisoning of Sergei and Yulia Skripal

On 12 March 2018, the UK government said that a Novichok agent had been used in an attack in the English city of
Salisbury Salisbury ( , ) is a city status in the United Kingdom, cathedral city and civil parish in Wiltshire, England with a population of 41,820, at the confluence of the rivers River Avon, Hampshire, Avon, River Nadder, Nadder and River Bourne, Wi ...
on 4 March 2018 in an attempt to kill former
GRU Gru is a fictional character and the main protagonist of the ''Despicable Me'' film series. Gru or GRU may also refer to: Arts and entertainment * Gru (rapper), Serbian rapper * Gru, an antagonist in '' The Kine Saga'' Organizations Georgia (c ...
officer Sergei Skripal and his daughter Yulia. British
Prime Minister A prime minister or chief of cabinet is the head of the cabinet and the leader of the ministers in the executive branch of government, often in a parliamentary or semi-presidential system. A prime minister is not the head of state, but r ...
Theresa May Theresa Mary May, Baroness May of Maidenhead (; ; born 1 October 1956), is a British politician who served as Prime Minister of the United Kingdom and Leader of the Conservative Party from 2016 to 2019. She previously served as Home Secretar ...
said in Parliament: "Either this was a direct action by the Russian state against our country, or the Russian government lost control of its potentially catastrophically damaging nerve agent and allowed it to get into the hands of others." On 13 March the BBC asked
Vladimir Putin Vladimir Vladimirovich Putin (born 7 October 1952) is a Russian politician and former intelligence officer who has served as President of Russia since 2012, having previously served from 2000 to 2008. Putin also served as Prime Minister of Ru ...
if Russia was "behind the poisoning of" Skripal and he answered "Get to the bottom of it first then we can discuss it" while he delegated a spokesperson to claim that "a circus show in the British parliament" was the upshot.
Boris Johnson Alexander Boris de Pfeffel Johnson (born 19 June 1964) is a British politician and writer who served as Prime Minister of the United Kingdom and Leader of the Conservative Party (UK), Leader of the Conservative Party from 2019 to 2022. He wa ...
, the Foreign Secretary, refused to shake hands with Russian ambassador Alexander Yakovenko as he expressed "outrage" over the attack. On the next day, the UK expelled 23 Russian diplomats after the Russian government refused to meet the UK's deadline of midnight on 13 March 2018 to give an explanation for the use of the substance. Addressing the
United Nations Security Council The United Nations Security Council (UNSC) is one of the six principal organs of the United Nations (UN) and is charged with ensuring international peace and security, recommending the admission of new UN members to the General Assembly, an ...
on 15 March, Vassily Nebenzia, the Russian envoy to the UN, responded to the British allegations by denying that Russia had ever produced or researched the agents, stating: "No scientific research or development under the title Novichok were carried out." After the attack, 21 members of the emergency services and public were checked for possible exposure, and three were hospitalised. As of 12 March, one police officer remained in hospital. Five hundred members of the public were advised to decontaminate their possessions to prevent possible long-term exposure, and 180 members of the military and 18 vehicles were deployed to assist with decontamination at locations in and around Salisbury. Up to 38 people in Salisbury have been affected by the agent to an undetermined extent. Daniel Gerstein, a former senior official at the U.S.
Department of Homeland Security The United States Department of Homeland Security (DHS) is the U.S. federal executive department responsible for public security, roughly comparable to the interior, home, or public security ministries in other countries. Its missions invol ...
, said it was possible that Novichok nerve agents had been used before in Britain to assassinate Kremlin targets, but had not been detected: "It's entirely likely that we have seen someone expire from this and not realised it. We realised in this case because they were found unresponsive on a park bench. Had it been a higher dose, maybe they would have died and we would have thought it was natural causes." On 20 March 2018, Ahmet Üzümcü, Director-General of the OPCW, said that it would take "another two to three weeks to finalise the analysis" of samples taken from the poisoning of Skripal. On 3 April 2018, the Defence Science and Technology Laboratory announced that it was "completely confident" that the agent used was Novichok, although they still did not know the "precise source" of the agent. Experts said that their findings did not challenge the conclusions by UK government: "We provided that information to the Government who have then used a number of other sources to come to the conclusions that they have." On 12 April 2018 the OPCW announced that their investigations agreed with the conclusions made by the UK about the identity of the chemical used. By September 2018, two Russian "tourists", " Alexander Petrov" and " Ruslan Boshirov", had been identified as suspects. They told Margarita Simonyan, the chief editor of RT television, in an interview that they both worked in the sports nutrition business and that: "Those are our real names.. We're afraid to go out, we fear for ourselves, our lives and lives of our loved ones." The
Crown Prosecution Service The Crown Prosecution Service (CPS) is the principal public agency for conducting criminal prosecutions in England and Wales. It is headed by the Director of Public Prosecutions. The main responsibilities of the CPS are to provide legal adv ...
announced enough evidence was obtained by that date "to convict the two men" of the attack, although it did not apply to Russia "for their extradition because Russia does not extradite its own nationals. ..However, a
European Arrest Warrant The European Arrest Warrant (EAW) is an arrest warrant valid throughout all member states of the European Union (EU). Once issued, it requires another member state to arrest and transfer a criminal suspect or sentenced person to the issuing stat ...
has been obtained in case they travel to the EU". In February 2019, the
Bellingcat Bellingcat (stylised bell¿ngcat) is a Netherlands-based investigative journalism group that specialises in fact-checking and open-source intelligence (OSINT). It was founded by British citizen journalist and former blogger Eliot Higgins in Ju ...
website published precise allegations that identified
GRU Gru is a fictional character and the main protagonist of the ''Despicable Me'' film series. Gru or GRU may also refer to: Arts and entertainment * Gru (rapper), Serbian rapper * Gru, an antagonist in '' The Kine Saga'' Organizations Georgia (c ...
Major Denis Vyacheslavovich Sergeev as a man who travelled in March 2018 to London under the false identity of Sergei Fedotov. It is claimed with detailed photograph evidence, and phone, travel, passport, and motoring database records that GRU Colonels Alexander Mishkin and
Anatoly Chepiga Anatoly Vladimirovich Chepiga (, born 5 April 1979) is a Colonel (Eastern Europe), colonel in the Russian General Staff's Main Directorate (also known as GRU (Russian Federation), GRU), the military intelligence service of the Russia, Russian ...
assumed the identities of Petrov and Boshirov, and placed the poison on Skripal's doorknob. On 28 June 2019, it was reported that Sergeyev received instructions from his GRU superior by cell phone on more than ten occasions during his UK visits.


Poisoning of Charlie Rowley and Dawn Sturgess

On 30 June 2018, Charlie Rowley and Dawn Sturgess were found unconscious at a house in
Amesbury Amesbury () is a town and civil parish in Wiltshire, England. It is known for the prehistoric monument of Stonehenge which is within the parish. The town is claimed to be the oldest occupied settlement in Great Britain, having been first settl ...
,
Wiltshire Wiltshire (; abbreviated to Wilts) is a ceremonial county in South West England. It borders Gloucestershire to the north, Oxfordshire to the north-east, Berkshire to the east, Hampshire to the south-east, Dorset to the south, and Somerset to ...
, about eight miles from the Salisbury poisoning site. On 4 July 2018, police said that the pair had been poisoned with the same nerve agent as ex-Russian spy Sergei Skripal. On 8 July 2018, Sturgess died as a result of the poisoning. Rowley regained consciousness and began recovering in hospital. He told his brother Matthew the nerve agent had been in a small perfume or aftershave bottle, which they had found in a park about nine days before spraying themselves with it. The police later closed and fingertip-searched Queen Elizabeth Gardens in Salisbury.


Poisoning of Emilian Gebrev

In the aftermath of the Skripal poisoning, investigative journalists were able to track some of the people involved also in Bulgaria. This is how another suspected poisoning case dating back to April 2015 during their stay in the country was linked to the Novichok nerve agent. The victim was the Bulgarian arms dealer Emilian Gebrev, who shared two hypotheses why he might have been attacked: The first one links to the fact that his arms manufacturing company Dunarit exports defense equipment to Ukraine. The other one relates to an attempt by an offshore company to take over Dunarit. The takeover attempt was ultimately linked to the influential Bulgarian politician and oligarch
Delyan Peevski Delyan Slavchev Peevski (, born 27 July 1980) is a Bulgarian politician and Oligarchy, oligarch, Sanctions (law), sanctioned by the Global Magnitsky Act, by the United Kingdom, UK and the United States for corruption, bribery and embezzlement. ...
who has historically been funded by Russia's state-owned
VTB Bank VTB Bank (; formerly known as ''Vneshtorgbank'', , lit. 'International Trade Bank') is a Russian majority state-owned bank headquartered in various federal districts of Russia; its legal address is registered as St. Petersburg. As of 2022, ...
. In November 2023 Bulgaria sought the extradition of three Russian
GRU Gru is a fictional character and the main protagonist of the ''Despicable Me'' film series. Gru or GRU may also refer to: Arts and entertainment * Gru (rapper), Serbian rapper * Gru, an antagonist in '' The Kine Saga'' Organizations Georgia (c ...
officers, Sergey Fedotov, Georgi Gorshkov and Sergey Pavlov, suspected of the poisoning incident. Sergei Fedotov was also the alias used by one of the assassins in the Salisbury poisonings.


Poisoning of Alexei Navalny

On 20 August 2020, Russian opposition leader
Alexei Navalny Alexei Anatolyevich Navalny (, ; 4 June 197616 February 2024) was a Russian Opposition to Vladimir Putin in Russia, opposition leader, anti-corruption in Russia, corruption activist and political prisoner. He founded the Anti-Corruption Found ...
fell ill during a flight from
Tomsk Tomsk (, ) is a types of inhabited localities in Russia, city and the administrative center of Tomsk Oblast in Russia, on the Tom (river), Tom River. Population: Founded in 1604, Tomsk is one of the oldest cities in Siberia. It has six univers ...
to
Moscow Moscow is the Capital city, capital and List of cities and towns in Russia by population, largest city of Russia, standing on the Moskva (river), Moskva River in Central Russia. It has a population estimated at over 13 million residents with ...
. The plane made an emergency landing in
Omsk Omsk (; , ) is the administrative center and largest types of inhabited localities in Russia, city of Omsk Oblast, Russia. It is situated in southwestern Siberia and has a population of over one million. Omsk is the third List of cities and tow ...
, where Navalny was hospitalized and put in a medically induced coma. His family suspected his illness was caused by a poison put into a cup of tea he drank before the flight. He was evacuated to the
Charité The Charité – Universitätsmedizin Berlin (Charité – Berlin University of Medicine; ) is Europe's List of hospitals by capacity, largest university hospital, affiliated with Humboldt University of Berlin, Humboldt University and the Free ...
hospital in
Berlin Berlin ( ; ) is the Capital of Germany, capital and largest city of Germany, by both area and List of cities in Germany by population, population. With 3.7 million inhabitants, it has the List of cities in the European Union by population withi ...
, Germany, the following day. On 2 September, the German government said that it had "unequivocal evidence" that Navalny was poisoned by a Novichok agent after tests at a German military lab and had called on the Russian government for an explanation, with labs in France and Sweden corroborating the findings. On 4 September, the
North Atlantic Council The North Atlantic Council (NAC) is the principal political decision-making body of the North Atlantic Treaty Organization (NATO), consisting of permanent representatives of its member countries. It was established by wikisource:North Atlantic ...
was briefed by the German representative on the "appalling assassination attempt on" Navalny. In a post-meeting press conference, Secretary-General
Jens Stoltenberg Jens Stoltenberg (; born 16 March 1959) is a Norwegian politician from the Labour Party. Since 2025, he has been the Minister of Finance in the Støre Cabinet. He has previously been the prime minister of Norway and secretary general of NATO. ...
said that NATO allies "agree that Russia has serious questions it must answer", that the OPCW needed to conduct an impartial investigation, that "those responsible for this attack must be brought to justice" and called on Russia to "provide complete disclosure of the Novichok programme to the OPCW." Navalny had been out of his coma since 7 September. On 6 October, the OPCW confirmed the presence of a
cholinesterase inhibitor Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine by cholinesterase. This increases the amount of the acetylcholine or butyryl ...
from the Novichok group in Navalny's blood and urine samples. At the same time, the OPCW report clarified that Navalny was poisoned with a new type of Novichok, which was not included in the list of controlled chemicals of the
Chemical Weapons Convention The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
.


See also

* Poison laboratory of the Soviet secret services *
Russia and weapons of mass destruction The Russian Federation is known to possess or have possessed three types of weapons of mass destruction: nuclear weapons, biological weapons, and chemical weapons. It is one of the five nuclear-weapon states recognized under the Treaty on the ...


List of Novichok agents

* A-230 * A-232 * A-234 * A-242 * A-262 (Novichok-7) * C01-A035 * C01-A039 * C01-A042


References


Explanatory notes


Citations


General and cited references

* * * * * * * * * * * * * * *


Further reading

*


External links

* * {{Authority control Acetylcholinesterase inhibitors Cold War weapons of the Soviet Union Nerve agents Organophosphates Science and technology in the Soviet Union Soviet chemical weapons program Soviet inventions