Anti-Viral Drug Backfires: COVID Drug Linked to Viral Mutations That Spread
Freeman writes:
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.
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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.
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When molnupiravir was authorized in the US, there was concern about its potential to cause mutations in people's DNA, rather than the virus. For this reason, it is not recommended for use in pregnant people. But the new data gives birth to more concern about mutations. And this risk is coupled with lackluster efficacy data. In a final data analysis for the Food and Drug Administration, molnupiravir's maker, Merck, combined two sets of trial data to come up with an estimate of just 30 percent efficacy at preventing hospitalization and death.
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FDA advisers summarized the data at the time as "not overwhelmingly good" and "modest at best." They voted in favor of authorizing the drug in a narrow 13 to 10 vote. The drug has never gained a foothold in Europe. Earlier this year, the European Medicines Agency refused to issue marketing authorization for molnupiravir. Upon the EMA's rejection, Merck said it was confident of the drug's role in fighting COVID-19 and that it would appeal the decision. In addition to the US, molnupiravir is approved for use in over two dozen countries, including Australia, China, Japan, and the UK, though use of the drug has been scaled back in many places.
Journal Reference:
Sanderson, T., Hisner, R., Donovan-Banfield, I. et al. A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes. Nature (2023). https://doi.org/10.1038/s41586-023-06649-6
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