Antiviral drug molnupiravir 'linked to mutations' in the virus

Belongs to a class of drugs designed to make the virus mutate so much it is fatally weakened

A doctor holds a Molnupiravir pill for the treatment of Covid. Getty Images
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An antiviral drug designed to treat Covid-19 could be causing mutations in the virus that are spreading in the community, according to a new study.

Molnupiravir, one of the first antivirals available during the pandemic, was widely adopted in many countries, including the UK, which was the first to approve it.

It belongs to a class of drugs designed to make the virus mutate so much it is fatally weakened and unable to replicate.

But scientists continuing to monitor Covid recently found changes in the virus which looked very different from typical patterns of mutations.

They found those changes, which increased in 2022 when the drug was first introduced, were “strongly associated” with people who had taken molnupiravir.

Theo Sanderson, lead author and postdoctoral researcher at the Francis Crick Institute, told The National the discovery will be useful in assessing the "risks and benefits" of the drug.

He said: "Our data doesn't quantify what this means in terms of risk.

"That's a pretty hard thing to predict. But what our data shows is that this treatment can give rise to significantly mutated viruses which are still viable. That is the useful discovery.

"There are some viruses which survive treatment with a significant number of mutations."

He said the process is different to that of what happens when bacteria develops resistance to antibiotics.

"[In this case, molnupiravir] is specifically acting to create mutations, whereas in antibiotics there are mutations spontaneously occurring that give resistance to the antibiotics."

He said antiviral drugs are still necessary, because some people struggle to clear the virus and get very sick from it.

"The possibility of persistent antiviral-induced mutations needs to be taken into account for the development of new drugs which work in a similar way," he said.

"Our work shows that the unprecedented size of post-pandemic sequence datasets, collaboratively built by thousands of researchers and healthcare workers around the world, creates huge power to reveal insights into virus evolution that would not be possible from analysis of data from any individual country."

The study, by researchers at the Francis Crick Institute, the University of Cambridge, Imperial College London, the University of Liverpool, the University of Cape Town and the UK Health Security Agency (UKHSA), also found the mutations were more likely in older age groups consistent with the use of the antivirals to treat people who are more at risk.

"Molnupiravir is one of a number of drugs being used to fight Covid-19,” said Christopher Ruis from the department of medicine at the University of Cambridge, which was involved in the research.

"But what we've found is that in some patients this process doesn't kill all the viruses, and some mutated viruses can spread."

In England, the researchers analysed treatment data and found that at least 30 per cent of the events involved the use of molnupiravir.

The researchers said although the drug is not immediately dangerous to people taking it, the study may have important implications for the future direction of the pandemic.

To study how mutations occur, scientists look at their mutational signature - a preference for mutations to occur at particular points in the virus.

Researchers involved in the study said there was a close match between the signature seen in mutational events and the signature in clinical trials of molnupiravir.

They also saw signs of onward transmission from one person to another, although no established variants of concern are currently linked to this.

According to the experts, it is also important to consider that chronic Covid infections, which molnupiravir is used for, can themselves result in new mutations.

Stephen Griffin, professor of cancer virology, University of Leeds, said: "This paper is an incredibly important, well-conducted piece of research.

"The findings are of critical value to our understanding of how the use of this specific antiviral drug could have been better implemented, but also reminds us of more general aspects of good practice and antimicrobial stewardship.

"It is worth noting that the use of this drug is not immediately dangerous to individuals taking it, but these findings have important implications for the future direction of the pandemic."

Updated: September 25, 2023, 5:14 PM