A drug used to treat covid-19 appears to be driving the evolution of the SARS-CoV-2 coronavirus, according to an analysis of the 15 million viruses sequenced around the world so far. The analysis found around 900 viruses with distinctive patterns of mutation that probably arose in people being treated with the drug molnupiravir. In at least a few cases, these viruses appear to have spread from the person being treated to others, but no variants of concern have any of these patterns.
鈥淭he signal is pretty clear and there aren鈥檛 variants of concern that have those signals,鈥� says at the Francis Crick Institute in London.
Molnupiravir works by inducing so many mutations in RNA viruses, such as SARS-CoV-2, as they replicate in a person鈥檚 body that the viruses lose the ability to replicate and die out. But before the viruses are eliminated from a person鈥檚 body, there is a risk of them spreading to others.
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A few biologists think the risk of these mutagenic drugs generating potentially dangerous new variants outweighs their benefits. Animal studies suggest molnupiravir , which is why it isn鈥檛 given during pregnancy, or if a potential recipient is trying to get pregnant or is breastfeeding.
Despite these concerns, regulatory agencies in many countries, including the US and UK, have approved molnupiravir for treating covid-19.
Sanderson, who carried out the analysis with his colleagues, says there are several lines of evidence supporting their conclusions. For starters, molnupiravir induces distinct types of mutation in the genomes of RNA viruses.
In countries that began using the drug in 2022, there was a rise in the number of viruses with these distinctive changes. 鈥淭hese sequences were much more likely to be observed in countries that use molnupiravir and particularly in the countries that use the most molnupiravir,鈥� says Sanderson.
What鈥檚 more, the team was able to check if the viruses sequenced in the UK came from people treated with the drug. They found that 31 per cent of variants with the distinctive pattern came from treated people, whereas just 0.04 per cent of the overall sequenced viruses came from treated individuals.
It is expected that molnupiravir will mutate the viruses in those being treated. The issue is whether those mutated viruses spread to other people. In most cases, the team couldn鈥檛 establish this. However, the researchers did identify a few clusters, including one in Australia, where there seemed to have been spread from person to person. 鈥淲e provide some cases where that鈥檚 very clear,鈥� says Sanderson.
Whether this could create dangerous new variants is unclear, he says. 鈥淥ur data doesn鈥檛 say how likely that is, but it鈥檚 clearly something that needs consideration.鈥�
鈥淚 think the most interesting question is: does treatment generate more new mutations in the population than non-treatment?鈥� says at Harvard University. In a study published last month, he and his colleagues .
A spokesperson for Merck, which makes molnupiravir, says that the study relies on circumstantial associations. 鈥淭he authors assume these mutations were associated with viral spread from molnupiravir-treated patients without documented evidence of that transmission鈥� Furthermore, these sequences were uncommon and were associated with sporadic cases.鈥�
The Merck spokesperson pointed to a review by the US Food and Drug Administration (FDA) of Sanderson鈥檚 initial findings earlier this year. 鈥淲hile it is plausible that [molnupiravir] use could contribute to mutational patterns in SARS-CoV-2 sequences, there are some uncertainties鈥︹�� . 鈥淎 causal relationship鈥� has not yet been established.鈥�
The memorandum also points out that the risk of treatments triggering the evolution of new variants isn鈥檛 limited to mutagenic drugs. Conventional drugs and antibodies put pressure on viruses to evolve to evade the treatment. The study 鈥渄oes not change the review team鈥檚 overall risk assessment鈥�, the memorandum concludes.
Nature
