Molnupiravir Associated with SARS-CoV-2 Virus Unusual Mutations

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Molnupiravir Associated with SARS-CoV-2 Virus Unusual Mutations

COVID-19 Drug Molnupiravir Found to Be Associated with SARS-CoV-2 Virus Unusual Mutations

Researchers have discovered a connection between the antiviral drug molnupiravir and specific mutations of the SARS-CoV-2 virus.

While molnupiravir is designed to induce mutations to weaken the virus, the study found different mutation patterns among individuals who have taken the drug. These mutations are particularly prevalent in older populations and regions with higher molnupiravir usage.

A study has revealed a link between the antiviral drug molnupiravir and various SARS-CoV-2 mutations, emphasizing the need for careful evaluation in drug development.

Researchers from the Francis Crick Institute, University of Cambridge, Imperial College London, University of Liverpool, University of Cape Town, and the UK Health Security Agency (UKHSA) have identified a connection between the antiviral drug molnupiravir, used to treat COVID-19 infections, and patterns of variation in the SARS-CoV-2 virus.

The mechanism of molnupiravir involves inducing mutations in the virus’s genetic information or genome during the replication process. Many of these mutations disrupt or kill the virus, reducing viral load in the body. It was one of the first antiviral drugs to be introduced during the COVID-19 pandemic and has been widely adopted by many countries.

In a study published today (September 25th) in the journal “Nature,” scientists used global sequencing databases to map the variations of the SARS-CoV-2 virus over time. They analyzed a family tree composed of 15 million SARS-CoV-2 virus sequences, allowing them to see which mutations occurred at each stage of the virus’s evolutionary history.

Unusual Mutation Patterns

While the virus has been continually mutating, researchers found mutation events in the global sequencing database that were distinct from the typical patterns of COVID-19 mutations, and these events were closely associated with individuals who had taken molnupiravir.

These mutations increased in 2022, coinciding with the introduction of molnupiravir. They were also more likely to occur in older populations, aligning with the practice of using antiviral drugs to treat high-risk individuals and with countries known for higher molnupiravir usage. In the UK, researchers analyzed treatment data and found that at least 30% of events were associated with molnupiravir usage.

COVID-19 Drug Molnupiravir Found to Be Associated with SARS-CoV-2 Virus Unusual Mutations

Comparison of global sequencing databases with known data from patients treated with molnupiravir showed similar mutation patterns (mutations from C to T and from G to A). Image Source: Theo Sanderson, “Nature” (2023).

The cause of these mutation events can be tracked by observing their “mutation signature,” with mutations favoring specific sequences in the genome. Researchers found that the features of these mutation events closely matched those observed in molnupiravir clinical trials.

Researchers also identified some small mutation clusters, indicating that these mutations could be transmitted from one individual to another, although no concerning mutations related to this feature have been discovered thus far.

Implications and Expert Insights

Understanding the impact of molnupiravir treatment on the risk of new mutations and any potential implications for public health is challenging. It is equally important to consider that chronic COVID-19 infections themselves can lead to new mutations, and molnupiravir is used to treat chronic COVID-19 infections.

Theo Sanderson, the lead author of the paper and a postdoctoral researcher at the Francis Crick Institute, stated, “COVID-19 continues to have a significant impact on human health, with some individuals struggling to clear the virus. Therefore, we must develop drugs aimed at reducing the duration of infection. However, our evidence suggests that a specific antiviral drug, molnupiravir, can also lead to new mutations, increasing the genetic diversity of the surviving viral population.”

“Our findings contribute to ongoing assessments of the risks and benefits of molnupiravir treatment. When developing new drugs that operate in a similar manner, the possibility of antiviral-induced mutations must be considered. Our work highlights the unprecedented scale of sequencing datasets generated by thousands of researchers and healthcare workers worldwide, which have the potential to reveal the truth about virus evolution and cannot be achieved by analyzing data from any single country.”

Christopher Ruise, from the Department of Medicine at the University of Cambridge, said, “Molnupiravir is one of several drugs used to combat COVID-19. It belongs to a class of drugs that can induce severe mutations in the virus, leading to its lethal weakening. However, we found that in some patients, this process does not kill all the virus, and some mutant viruses continue to spread. This must be considered when assessing the overall benefits and risks of molnupiravir and similar drugs.”