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widely used COVID-19 drug may be driving the appearance of new SARS-CoV-2 variants, sparking concerns it could prolong and even reinvigorate the pandemic. The drug, molnupiravir, produced by Merck & Co., is designed to kill the virus by inducing mutations in the viral genome. A survey of viral genomes reported in a new preprint, however, suggests some people treated with the drug generate novel viruses that not only remain viable, but spread.
“It’s very clear that viable mutant viruses can survive [molnupiravir treatment] and compete [with existing variants],” says virologist William Haseltine, chair of ACCESS Health International, who has repeatedly raised concerns about the drug. “I think we are courting disaster.” But a Merck spokesperson disputes that the drug has led to the emergence of widely circulating variants, and some researchers downplayed the significance of molnupiravir-caused mutations. “Right now, it’s much ado about nothing,” says Raymond Schinazi, a medicinal chemist at the Emory University School of Medicine, noting that with SARS-CoV-2 infecting millions of people worldwide, the virus is naturally mutating at a fast clip.
Authorized in the United Kingdom and the United States in late 2021, molnupiravir was the first oral antiviral approved anywhere to fight COVID-19. It has since been authorized in dozens of other countries. In 2022, Merck estimated global sales of the compound at more than $5 billion. Though that is well below the $18.9 billion in 2022 sales for Paxlovid, another oral SARS-CoV-2 antiviral, molnupiravir remains widely popular in certain countries.
From the start, however, Haseltine and others worried about the drug’s mechanism, which involves introducing so many mutations into the viral genome that it can no longer reproduce. One concern was that the drug might mutate not just the coronavirus, but the DNA of people receiving it—a side effect that has not been seen so far. Another was that mutated virus would survive and propagate—and perhaps turn out to be more transmissible or virulent than before. Before the U.S. Food and Drug Administration authorized the drug, a Merck spokesperson called the worry “an interesting hypothetical concern.”
