Novichok: how does the deadly nerve agent work?

On the 22 March, detective sergeant Nick Bailey was discharged from hospital following exposure to Novichok in the Salisbury attack.

Sgt Bailey had been seriously ill after responding to the already infamous assassination attempt on Sergei Skripal and his daughter Yulia on the 4 march. 

Speculations on the origin of the attack aside, one question being asked is what exactly is Novichok, and how does it work?

Novichok, or “New comer”, is a class of nerve agents which Russian scientists began developing in the 1970s. However, the Novichok development programme had remained a carefully guarded Russian secret until 1992, when Vil Mirzayanov, a former Russian military chemist, exposed the secret to the world.  

Following this, a few Novichok nerve agents have become known to the scientific community, but there’s no way of knowing how many others Russia has developed and kept hidden.

In 2008, Mirzayanov wrote a memoir which mentioned the Novichok nerve agents, explaining that they are similar in structure to other nerve agents such as Sarin. He went on to write that, like this other class of nerve agents, they kill by binding to and inhibiting acetylcholinesterase.

Acetylcholinesterase is an enzyme in the synapses between nerves which breaks down the neurotransmitter acetylcholine. By inhibiting this breakdown, Novichok agents allow acetylcholine to build up and alter signals to the muscles, heart, and lungs, eventually leading to death.

Currently, nerve agent victims are given two drugs for treatment: Atropine, which blocks the receptors that acetylcholine acts on and therefore tries to prevent some of the aberrant signalling, and a drug from the Oxime class which tries to pry the nerve agent out from acetylcholinesterases before they bind permanently.

So, if we already have a treatment, why are Novichok nerve agents such a problem?

It’s to do with how Oximes work. Oximes are also a class, and each one works differently. Their effectiveness depends on the nerve agent’s chemical structure, and how it interacts with its target. Different Oximes are better at targeting different nerve agents – think of it as the correct antidote needed for a poison – and so the right one is needed to cure the victim.

However, as so little is known about the nerve agent used – even down to which specific chemical it is – there’s no knowing which Oxime is best, at what concentrations, or which method of delivery.

As a result, doctors are having to treat victims as broadly as possible, making it less likely that they’re using the most effective treatment.

Additionally, the few known Novichok agents have been engineered to include an alkyl amine group to allow them to target other enzymes in addition to acetylcholinesterase. As a result, unknown neurological effects may arise months or years down the line, thus making these agents even more dangerous.

Being discharged from hospital does not mean that Detective Seargant Bailey is out of the woods, but it is certainly a good sign in the short term.

Image credit: Wikimedia Commons

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