‘Wonderful’ Covid drug may cause virus to mutate uncontrollably amid fears it could spawn a new variant

A Covid drug hailed as a game-changer could cause the virus to mutate, scientists warned today.

Molnupiravir will be given to thousands of vulnerable Brits who have tested positive, such as those suffering from cancer or liver and kidney disease.

The antiviral, made by US pharmaceutical giant Merck, protects against serious illness by forcing mutations in the virus that fatally weaken it.

However, in some cases these mutations do not kill the virus, say researchers at 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 the key now is to find out whether mutations triggered by molnupiravir can make the pandemic-causing virus more transmissible or more severe, or allow it to evade immunity from previous infections or vaccinations.

Some have even warned that its use could lead to the emergence of new variants, although the manufacturer has dismissed such fears.

Molnupiravir is being distributed in the UK to vulnerable adults who have tested positive for Covid, such as cancer, liver and kidney patients

Molnupiravir, sold under the brand name Lagevrio, works by preventing the growth and spread of Covid 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 that the drug – which was rolled out to patients in the UK from December 2021 and is described as an “excellent addition” to the country’s “armament against Covid” – reduces the risk of being admitted or suffering from Covid to die, halved.

The team, which included scientists from the University of Cambridge, Imperial College London, the University of Liverpool and the University of Cape Town, found that molnupiravir works by triggering 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 killed, meaning they can infect others with the molnupiravir mutant virus.

They examined a family tree of 15 million Covid sequences collected from global databases to map its mutations over time.

Covid is constantly mutating and most have little or no influence on the properties of the virus, such as its transmissibility or the severity of the infection it causes.

However, in a study published in the journal Nature, researchers said they discovered changes to the virus that looked very different from the expected patterns.

These mutations were closely linked to people who had taken molnupiravir.

The team found that the frequency of these mutations increased in 2022 as adoption gained momentum.

The unusual changes in the virus were also more common in older people – who are more likely to be given the drug – in countries known to have high molnupiravir use, and in samples taken as part of clinical trials of the drug became.

According to the researchers, three in 10 of the abnormal mutations seen in England were in those given the drug.

The team also discovered clusters of strange mutations, suggesting that the optimized version of the virus was passed on to others. However, they found that no variants of concern were linked to the mutations caused by the drug.

It is difficult to understand whether molnupiravir has the risk of triggering new variants or whether they could threaten public health.

And chronic Covid infections, against which the drug is used, can also trigger new mutations.

Theo Sanderson, lead study author and researcher at the Francis Crick Institute, said: “It is important that we develop drugs aimed at shortening the duration of the infection.”

“But our evidence shows that a specific antiviral drug, molnupiravir, also leads to new mutations and increases genetic diversity in the surviving virus population.”

He said that when developing drugs that work similarly to molnupiravir, drugmakers must consider the risk that the drug will trigger mutations in a virus.

Christopher Ruis, a researcher at the University of Cambridge, said the results showed that molnupiravir did not kill all of the virus in some patients and that the mutated virus could spread.

“This is important to consider when assessing the overall benefits and risks of molnupiravir and similar drugs,” he said.

Taking molnupiravir as four capsules twice daily for five days has not been associated with serious side effects, although some patients report experiencing headaches, nausea and dizziness. In rare cases an allergic reaction may occur.

The antiviral, made by US pharmaceutical giant Merck, protects against serious illness by forcing mutations in the virus that fatally weaken it

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 heavily molnupiravir-mutated viruses were able to spread.

“But it is not clear whether any of the transmitted viruses contained mutations that would change their behavior – for example, if they were more or less transmissible, more pathogenic, or less susceptible to our immunity.” “That’s a key question to ask clarify.”

Dr. Chris Illingworth, senior lecturer in virology at the University of Glasgow, said there was a “Caution is advised before simply stopping drug use.

“It is believed that most mutations make the virus less dangerous, rather than increasing it. Therefore, we cannot yet say that the use of molnupiravir has been harmful to human health,” he said.

Some experts were quick to point out molnupiravir’s potential to trigger worrisome mutations when it first hit headlines in late 2021 – and even called its continued use “disturbing.”

Professor Stephen Griffin, an infectious disease expert at the University of Leeds, said that in most cases Covid does not mutate and spread when using molnupiravir.

“However, as we have seen recently, with [the BA2.86 Covid variant]“Covid evolution sometimes makes ‘jumps’ and anything that might contribute to that is a bad idea,” he said.

Professor Griffin added: “What remains certain, however, is that we must remain vigilant to the ongoing changes and leaps in the evolution of SARS-COV-2, which is becoming increasingly difficult to track due to reductions in testing and surveillance.”

A Merck spokesman said: “Clinical and preclinical data show that molnupiravir impairs viral replication and reduces viral shedding, which would reduce the risk of transmission.”

“The authors of Sanderson et al. Manuscript based their research on divergent global database SARS-CoV-2 sequences that capture specific mutation patterns present in the virus populations.

“The authors believe that these mutations were associated with viral spread in patients treated with molnupiravir, without any documented evidence of this transmission.”

“Instead, the authors rely on circumstantial relationships between the region from which the sequence was identified and the time frame of sequence collection in countries where molnupiravir is available to draw their conclusions.”

“In addition, these sequences were uncommon and were associated with sporadic cases.” As noted by the authors, there are limitations to the analyzes performed in this study, which are described in more detail in the manuscript. These data must be considered in the context of all available clinical and non-clinical molnupiravir data.”