Image showing the SARS-CoV-2 virus being attacked by a COVID-19 antiviral drug such as molnupiravir

The antiviral drug molnupiravir, used extensively to treat SARS-CoV-2 infection, induces genetic mutations in the virus that could lead to new variants emerging, according to new research led by the Francis Crick Institute in London.

So far there is no direct evidence of molnupiravir use leading to a new and potentially more harmful form of the virus behind COVID-19 impacting human populations, but the new study shows it is something to consider for clinicians and researchers when prescribing the antiviral and when developing similar drugs in the future.

“New variants of SARS-CoV-2 are generated through acquisition of mutations that enhance properties including immune evasion and intrinsic transmissibility,” write Theo Sanderson, a researcher at the Francis Crick Institute who led the study, and colleagues in the journal Nature.

“The impact of molnupiravir treatment on the trajectory of variant generation and transmission is difficult to predict.”

Sanderson and co-investigators analyzed large databases containing over 15 million SARS-CoV-2 viral genomes and searched for mutations linked to molnupiravir treatment. A particular mutational profile was linked to the drug and was more widespread in countries where use of molnupiravir was widespread after it was introduced in 2022 such as the U.K., U.S.A, and Japan, but less common in countries where the antiviral was not approved such as Canada.

Molnupiravir is recommended for patients with mild-moderate COVID-19 who are at high risk of developing more severe disease and being hospitalized and who are not able to take other treatments due to access problems or other clinical issues. Its mode of action is to induce mutations in the viral genome as it replicates to reduce the number of viable new virus particles being formed.

“What we’ve found is that in some patients, this process doesn’t kill all the viruses, and some mutated viruses can spread. This is important to take into account when assessing the overall benefits and risks of molnupiravir and similar drugs,” said co-author Christopher Ruis, a researcher at the University of Cambridge, in a press statement.

“The possibility of persistent antiviral-induced mutations needs to be taken into account for the development of new drugs which work in a similar way,” added Sanderson.

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