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A. Navaln felt ill on August 20 after drinking tea at Tomsk airport. He was in a coma and was airlifted to the Charite Clinic in Berlin two days later. On Wednesday, hospital officials said he woke up from a coma and was “responding to verbal stimuli,” according to www.sciencemag.org.
Navaln’s defenders have accused the Russian authorities of poisoning the tea; recalling the practice of silencing Russian critics with toxic substances, the accusation does not seem broken.
Novičiok A234 was chosen to silence a former Russian spy, Sergei Skripal, in Salisbury (UK) in March 2018. In a refusal operation, two Russian intelligence officers attempted to assassinate his daughter, Julia, in an attempt to kill her Skripali, leaving a clear mark on the evidence. The targets of the operation survived, but then a random woman found a perfume bottle containing poison and died.
Investigators hope the Novičok poisoning site will be cleared
© PA Wire / Scanpix
The Salisbury scandal brought Novičiok to light. After Russian chemists shared some details about these highly poisonous NPMs in 1992 (there are at least seven of them), the US and allied authorities ended open discussions; Novičiok was classified. The negligent use of A234 in the UK sparked a public backlash. In October 2019, the parties to the Chemical Weapons Convention agreed to include Novičiok on the list of toxic substances, thus putting it within the scope of the convention. This provided the opportunity to investigate these “fourth generation” MNPs, as well as to develop antidotes and treatments.
Such diplomatic impulses did not deter the unknown invaders from Navalna. In an effort by Berlin doctors to save him, researchers at the Bundeswehr Institute for Pharmacology and Toxicology in Munich have identified the mysterious cause of the symptoms.
They knew clear objectives. Like other NPMs, Novičiok binds to acetylcholinesterase (AChE), an enzyme that breaks down the neurotransmitter acetylcholine at synapses.
Common symptoms of Novičiok poisoning include dizziness, shortness of breath, seizures; without medical intervention, the victims develop a coma. Red blood cell membranes contain AChE, which can detect a formed conjugate of Novičiok and AChE in blood samples, which scientists can detect with a mass spectrometer, says Palmer Taylor, a pharmacologist at the University of California, San Diego (UCSD ).
Novičiok can also bind to albumin, the most abundant protein in the blood. Conjugates of nerve paralyzing substances with blood serum albumin “are very useful markers” that can be detected at least a couple of weeks after poisoning, says Stefano Costanzi, chemist and non-proliferation analyst at American University in Washington, DC
A third candidate is a conjugate with butyrylcholinesterase (BChE), an enzyme that assembles NPM molecules in the blood. It would be easy to use an anti-BChE antibody that binds to the conjugate and says the protein.
Most of the Novičiok molecule would remain attached to one of the fragments and would be easily detected by mass spectrometry, says Oksana Lockridge, a toxicologist at the University of Nebraska Medical Center. “I have no doubt that the Bundeswehr group has used this method,” he says. “The portion of Novičiok bound to this enzyme is much larger than any other nerve paralyzing substance,” notes UCSD chemist Zoran Radić. If such a conjugate is detected, Novičiok would identify with “100% confidence,” says Lockridge, who is developing BChE as a prophylactic against NPM.
The Salisbury sample probably provided important information about Novičiok. The US government now “knows much more about the toxicity, detection and general properties of Novičiok,” says toxicologist Kamil Kuča of the Hradec Králové University in the Czech Republic. “They could share their results with ‘friends’, say Germany,” he says. And the work of chemical detectives from investigators at the US Defense Laboratory in Porton Downe has been able to accelerate the analysis of the Munich laboratory by “providing a set of appropriate protocols,” Radić said.
Furthermore, the main component, Novičiok himself, in Navalno’s body can be directly detected. “It’s easy to see that they build up in lipids,” says Radić. In an article published earlier this year in Heliyon, the Chemical and Biological Weapons Center of the US Army Combat Capabilities and Development Command showed that the three components of Novičiok are much more stable than other NPMs, and the strongest, A234, is about 1,000 times more stable than zarin.
This stability may be why these few known Novičiok victims respond so poorly to treatment: Novičiok’s fat cell supply can linger for more than a week. Another shady feature of Novičiok is his deadly attachment to AChE: he binds and blocks not one active center, like other NPMs, but two.
Novičiok’s structure is unique. It’s really different from other nerve paralyzing substances, “says Radić. As a result, oximes, antidotes that separate NPM from AChE and reactivate the enzyme, can be much less effective against Novičiok than against classical substances of this type, such as tsarina.
“There is no classified information on the reactivation of the Novičiok victims,” Radić said.
One researcher says that pralidoxime, an antidote used by US soldiers at risk of exposure to NPM, has helped Salisbury victims, but does not work by reactivating AChE.
Whoever organized the attack on Navalna, the incident and news of Novičiok’s resistance raise concerns about their threat. And while most NPMs are liquid, some Novičiok are also stable as an ultra-fine powder. “They are much easier to hide and store than classic nerve paralyzing substances,” says Radić, noting that it is easier for them to find themselves on the black market.
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