Research finds a link between antiviral drug for COVID-19 and SARS-CoV-2 mutations


Researchers from the Francis Crick Institute, University of Cambridge, Imperial College London, University of Liverpool, University of Cape Town and UKHSA have revealed a link between the antiviral drug called molnupiravir and a pattern of mutations responsible for COVID-19 infection. SARS-CoV-2 virus.

Molnupiravir works by causing mutations in the genetic information or genome of the virus 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.

In research published in Nature Today, scientists used global sequencing databases 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. Had taken.

With the introduction of molnupiravir, these mutations increased 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. In England, researchers analyzed treatment data and found that at least 30% 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.

The researchers 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.

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.

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 medicines that aim to shorten the duration of infection. But our evidence shows that a specific antiviral drug, molnupiravir, also results in new mutations, increasing genetic diversity in surviving viral populations.


Our findings are useful for ongoing evaluation of the risks and benefits of molnupiravir treatment. The possibility of persistent antiviral-induced mutations must be taken into account for the development of new drugs that work in a similar manner. Our work shows that the unprecedented size of the post-pandemic sequencing dataset, built collaboratively by thousands of researchers and health workers around the world, has greater power to reveal insights into the evolution of the virus than the analysis of any individual country’s data. Would not be possible. ,


Theo Sanderson, lead author and postdoctoral researcher, Francis Crick Institute

Christopher Ruis, of the Department of Medicine at the University of Cambridge, said: “Molnupiravir is one of a number of medicines being used to fight COVID-19. It belongs to a class of medicines that prevent the virus from spreading so may mutate such that it becomes fatally weakened. But we have found that in some patients, this process does not kill all the virus, and some mutated viruses may spread. We will assess the overall benefits and risks of molnupiravir and It is important to keep in mind the timing of similar medications.”

Source:

Francis Crick Institute

Journal Reference:

Sanderson, T., and others, (2023). Molnupiravir-associated mutational signatures in the global SARS-CoV-2 genome. Nature, doi.org/10.1038/s41586-023-06649-6.

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