Covid antiviral drug molnupiravir linked to virus mutation: study


Molnupiravir, a widely used COVID-19 antiviral drug, has been linked to the pattern of mutations in the SARS-CoV-2 virus, according to a study published in the journal Nature.

A team including researchers from the Francis Crick Institute and the University of Cambridge in the UK noted that molnupiravir works by causing mutations in the virus’s genetic information, or genome, during replication.

Many of these mutations will damage or kill the virus, thereby reducing the viral load in the body. It was one of the first antivirals available on the market during the COVID-19 pandemic and was widely adopted by many countries.

Scientists used a global sequencing database to map mutations in the SARS-CoV-2 virus over time. They analyzed a family tree of 15 million SARS-CoV-2 sequences to see which mutations had occurred at each point in the evolutionary history of each virus.

Although viruses mutate all the time, researchers identified mutational events in global sequencing databases that looked very different from the typical pattern of COVID-19 mutations, and they were strongly linked to individuals who took molnupiravir.

The researchers found that these mutations increased with the introduction of molnupiravir in 2022. They were also more likely to be seen in older age groups, consistent with the use of antivirals to treat people at higher risk, and in countries where molnupiravir use is higher.

The team analyzed treatment data in England and found that at least 30 percent of the events involved the use of molnupiravir.

The causes of mutational events can be determined by looking at their ‘mutation signature’: the preference of mutations to occur at particular sequences in the genome.

The researchers found a close match between the signature seen in these mutational events and the signature in clinical trials of molnupiravir.

They also observed small clusters of mutations that suggest onward transmission from person to person, although no established variants of concern are currently associated with this signature.

The researchers said it is difficult to understand the impact of molnupiravir treatment on the risks of new variants and any impact they may have on public health.

It is also important to consider that chronic Covid-19 infection, for which molnupiravir is used, may itself be the result of new mutations, he said.

Theo Sanderson, lead author of the study and postdoctoral researcher, said: “COVID-19 is still having a major impact on human health, and some people are having difficulty getting rid of the virus, so it is important that we develop such medicines. whose aim is to reduce the duration of infection.” At the Francis Crick Institute.

“But our evidence shows that a specific antiviral drug, molnupiravir, also results in new mutations, increasing genetic diversity in surviving viral populations,” Sanderson said.

The researchers said these findings are useful for ongoing evaluation of the risks and benefits of molnupiravir treatment.

He said the possibility of persistent antiviral-induced mutations must be taken into account in the development of new drugs that work in a similar manner.

“Molnupiravir is one of several drugs being used to fight COVID-19. ‘It belongs to a class of drugs that can mutate the virus so much that it becomes fatally weakened,’ said Christopher Ruis of the University of Cambridge.

“But we have found that in some patients, this process does not kill all the virus, and some mutated viruses may spread. It is important to keep this in mind when assessing the overall benefits and risks of molnupiravir and similar drugs.” Ruiz said.

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