Media release

From: Springer Nature

COVID-19: Molnupiravir linked to new SARS-CoV-2 mutational signatures

The antiviral drug molnupiravir may be driving a specific mutational profile in SARS-CoV-2, suggests a study published in Nature this week. Observations suggest the emergence of a mutational signature that corresponds with molnupiravir use. It is not clear whether the mutations affect tolerance to molnupiravir, but the findings may help further investigations of the effects of this drug on viral evolution.

Molnupiravir, which has been widely used as treatment for SARS-CoV-2 infection, acts by inducing mutations in the virus genome during replication, reducing the numbers of viable viral progeny. However, if the treatment does not fully clear SARS-CoV-2 infection there may be a risk of transmission of molnupiravir-associated mutations.

Theo Sanderson and colleagues investigated the mutational profile associated with molnupiravir treatment and the extent to which these mutations may have spread. Searching through global sequencing databases containing more than 15 million SARS-CoV-2 genomes, the authors identify specific mutations in sequences from 2022, after the introduction of molnupiravir treatment. Many of the countries in which these mutations were identified reported widespread use of molnupiravir in 2022, such as the UK, Australia, the USA and Japan. By contrast, countries that have not authorized the use of molnupiravir, such as Canada, had a lower number of these mutations in screened sequences.

These results indicate that molnupiravir treatment has produced a signature mutation profile that is identifiable in sequence databases, a finding that should be considered when assessing the effects and safety of this drug. However, whether molnupiravir might alter the trajectory of variant generation or transmission is difficult to predict, the authors note.