COVID-19 Antiviral Drug May Lead to SARS-CoV-2 Mutations

Scientists say viral mutations due to Molnupiravir use could spread from person to person.

Molnupiravir, developed by Merck & Co., Inc., is one of the earliest antiviral drugs introduced during the COVID-19 pandemic. It works by causing mutations in the virus's genetic information or genome during replication. These induced mutations often harm or kill the virus, which helps reduce the viral load within the body.

Still, some of these damaged viruses can survive and replicate, leading to a new SARS-CoV-2 mutation.

Despite concerns from virologists about the drug's potential to generate viral mutations, numerous countries began using Molnupiravir when it became available in 2021 and 2022 as a tool to combat COVID-19.

However, results from a study published on September 25 in Nature may have validated those concerns, as researchers unveiled a significant connection between Molnupiravir and a distinct pattern of mutations in the SARS-CoV-2 virus.

The link between Molnupiravir and SARS-CoV-2 mutations

Scientists from the United Kingdom and South Africa analyzed a family tree encompassing 15 million SARS-CoV-2 sequences. The researchers were able to pinpoint mutations that took place at various points in the virus's evolutionary history.

While viruses naturally undergo mutations, the researchers observed mutational events within the global sequencing database that differed from the typical SARS-CoV-2 mutation patterns. These atypical mutations were strongly linked to individuals treated with Molnupiravir.

In addition, the scientists found that the frequency of these mutations surged in 2022, coinciding with the widespread usage of the antiviral medication. Moreover, the mutations were also more prevalent in countries reporting high usage of the antiviral drug and among older individuals, which aligns with Molnupiravir's use to treat those at higher risk.

In England, for example, at least 30% of the observed mutations were associated with Molnupiravir use.

Moreover, the researchers found that mutational signatures associated with Molnupiravir use were similar to those observed in the drug's clinical trials.

The research team suggests that these mutated viruses have the potential to spread from person to person. However, there is currently no evidence that suggests transmission has occurred.

"Our findings show that Molnupiravir creates genetically divergent viruses capable not only of replicating but transmitting, with unknown consequences for the global public," said study author Ryan Hisner, a graduate student in bioinformatics at the University of Cape Town.

Hisner adds, "This should have been of greater concern when Molnupiravir was tested in clinical trials, and now that we have this evidence, regulators need to be proactive in monitoring virus sequencing databases for the effects of drugs that work by mutagenesis."