A Covid drug being hailed as a game-changer could cause the virus to mutate, scientists warned today.
Molnupiravir is being given to thousands of vulnerable Britons who test positive, such as patients battling cancer or liver and kidney disease.
The antiviral drug, made by US pharmaceutical giant Merck, protects against serious illness by forcing mutations into the virus that fatally weaken it.
However, in some cases these mutations do not kill the virus, say researchers from the Francis Crick Institute and the UK Health Security Agency (UKHSA).
Instead, a patient can remain infected with a mutated version of Covid and pass it on to others, according to the team’s analysis of millions of virus sequences.
Experts warned that it is now crucial to find out whether mutations caused by molnupiravir can make the pandemic-causing virus more transmissible or severe, or allow it to evade immunity from previous infections or vaccines.
Some have even warned that its use could lead to the emergence of new variants, although the manufacturer has allayed such fears.
Molnupiravir is being distributed to high-risk adults in Britain who have tested positive for Covid, such as cancer, liver and kidney patients
Molnupiravir, sold under the brand name Lagevrio, works by stopping Covid from growing and spreading in an infected person, keeping virus levels low.
This helps the body’s immune system control the infection, reducing the risk of severe symptoms and hospitalization.
Clinical trials suggest the drug – which was rolled out to patients in Britain from December 2021 and is described as an ‘excellent addition’ to the country’s ‘arsenal against Covid’ – halves the risk of hospitalization or death from Covid.
The team, made up of scientists from the University of Cambridge, Imperial College London, the University of Liverpool and the University of Cape Town, noted that molnupiravir’s effects are the result of causing a series of mutations in the virus.
Many of the mutations damage or kill the virus.
However, in some patients the virus is not completely cleared, meaning they can infect others with the molnupiravir mutated virus.
They examined a family tree of 15 million Covid sequences collected from global databases to map the mutations over time.
Covid is constantly mutating and most have little to no effect on the properties of the virus, such as how transmissible it is or the severity of the infection it causes.
However, in a study published in the journal Nature, researchers said they noticed changes in the virus that looked very different from expected patterns.
These mutations were strongly linked to people who had taken molnupiravir.
The team noted that the frequency of these changes increased in 2022, as the rollout accelerated.
The unusual changes in the virus were also more common in older people – who are more likely to receive the drug – in countries known to have high molnupiravir use and in samples taken during clinical trials of the drug .
According to the researchers, three in 10 of the abnormal mutations observed in England were among those given the drug.
The team also discovered clusters of strange mutations, indicating that the modified version of the virus had been passed on to others. However, they noted that no variants of concern are linked to the mutations that could be caused by the drug.
It is difficult to understand whether molnupiravir risks causing new variants or whether these could endanger public health.
And chronic Covid infections – which the drug is used to treat – can also cause new mutations.
Theo Sanderson, lead author and researcher from the Francis Crick Institute, said: ‘It is important that we develop drugs that aim to shorten the duration of infection.
‘But our evidence shows that a specific antiviral drug, molnupiravir, also leads to new mutations, increasing genetic diversity in the surviving virus population.’
He said drugmakers should consider the risk of the drug causing mutations in a virus when developing drugs that work in a similar way to molnupiravir.
Christopher Ruis, a researcher at the University of Cambridge, said the findings show that molnupiravir does not kill the entire virus in some patients and that the mutated virus can spread.
“This is important to consider when assessing the overall benefits and risks of molnupiravir and similar medications,” he said.
Molnupiravir, taken as four capsules twice a day for five days, has not been associated with serious side effects, although some patients report experiencing headaches, nausea and dizziness. In rare cases it can cause an allergic reaction.
The antiviral drug, made by US pharmaceutical giant Merck, protects against serious illness by forcing mutations into the virus that weaken it fatally
It was approved in the UK in November 2021 and in the US a month later.
Professor Jonathan Ball, a virologist at the University of Nottingham, said it was ‘surprising’ that the viruses highly mutated by molnupiravir were able to spread.
‘But what is not clear is whether any of the transmitted viruses contained mutations that would change the way they would behave – for example, if they were more or less transmissible, more pathogenic or less susceptible to our immunity. This is an important question to answer.”
Dr. Chris Illingworth, senior lecturer in virology at the University of Glasgow, said there is a ‘caution should be exercised before simply discontinuing use of the drug.”
‘You would expect that most mutations make the virus less rather than more dangerous. As such, we cannot yet say that the use of molnupiravir has been harmful to human health,” he said.
Some experts immediately pointed out that molnupiravir could cause worrying mutations when it first hit the news in late 2021. – and even labeled its continued use as ‘disturbing’.
Professor Stephen Griffin, an infectious disease expert at the University of Leeds, said that in most cases Covid will not mutate and spread if molnupiravir is used.
“But as we have seen recently with (the BA2.86 Covid variant), Covid evolution sometimes makes ‘leaps’, and anything that could help with that is a bad idea,” he said.
Professor Griffin added: ‘What remains certain, however, is that we must remain vigilant to the ongoing shifts and jumps in the evolution of SARS-COV-2, which are becoming increasingly difficult to track due to the reduction in testing and surveillance.”