A 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.
In one, researchers in Australia found evidence that molnupiravir treatment may be leading to new variants in immunocompromised patients. Because these patients’ immune systems have trouble clearing the virus, viral variants can accrue large numbers of mutations, possibly causing big leaps in viral behavior that can then be passed to others. (Researchers have speculated that Omicron and other SARS-CoV-2 variants evolved naturally in immunocompromised people.) Repeatedly sequencing SARS-CoV-2 genomes from nine patients, five of whom received the drug and four who did not, the researchers found that molnupiravir-treated individuals harbored an average of 30 new variants each within 10 days of the initial dose, far more than the untreated patients. “Our study demonstrates that this commonly used antiviral can ‘supercharge’ viral evolution in immunocompromised patients, potentially generating new variants and prolonging the pandemic,” the authors wrote in a 22 December 2022 preprint.