With every new infection, the pandemic coronavirus gets new chances to mutate and adapt, creating opportunities for the virus to evolve new variants that are better at dodging our immune systems and making us sicker.

Anti-viral drugs, such as Paxlovid and remdesivir, aim to halt this incessant evolution in individual patients—shortening illnesses, snuffing out opportunities for mutation, and reducing transmission. But one antiviral appears to be backfiring—allowing SARS-CoV-2 more opportunities to mutate.

According to a new peer-reviewed study in the journal Nature, the anti-viral drug dubbed molnupiravir is linked to specific SARS-CoV-2 mutation signatures that happened to spring up in 2022 when the drug was introduced.

The study’s authors—led by researchers at the Francis Crick Institute in London and the University of Cambridge—scanned through more than 15 million SARS-CoV-2 genome sequences found in global databases. They picked out unique mutation signatures that closely linked to signatures seen in viruses from patients known to have been treated with molnupiravir. These suspected molnupiravir-linked mutation signatures also matched those seen in viruses examined in a clinical trial of molnupiravir. Overall, the signatures appeared in older people, who are most likely to have been treated with an antiviral, and people in countries where molnupiravir has often been used.

Beyond simply finding molnupiravir-linked mutations, the researchers noted concerning features of them. The researchers found evidence that some of the molnupiravir-linked mutations were under positive selection—that is, they increased in frequency, suggesting that they were advantageous to the virus in some way. They also noted that some viruses with molnupiravir-linked mutations were passed on from person to person in clusters, which suggested onward transmission of these drug-induced mutations.

The findings indicate that “molnupiravir results in new mutations, increasing the genetic diversity in the surviving viral population,” Theo Sanderson, lead author and postdoctoral researcher at the Francis Crick Institute, said in a statement.

For now, there is no evidence that molnupiravir has contributed to the development of any of the most significant SARS-CoV-2 variants, such as omicron. And the clusters of transmission seen in the data are small. Still, Sanderson says the study’s finding is important for weighing the risks and benefits of molnupiravir, highlighting the “possibility of persistent antiviral-induced mutations.”

https://arstechnica.com/?p=1971307