"Abstract
The antiviral Molnupiravir (Lageviro) is widely used across the world to treat SARS-CoV-2 infection. Molnupiravir reduces viral replication by inducing mutations throughout the genome, yet in patients that do not clear the infection, the longer-term impact of the drug on virus evolution is unclear. Here, we used a case-control approach to monitor SARS-CoV-2 genomes through time in nine immunocompromised patients with five treated with Molnupiravir. Within days of treatment, we detected a large number of low-frequency mutations in patients and that these new mutations could persist and, in some cases, were fixed in the virus population. All patients treated with the drug accrued new mutations in the spike protein of the virus, including non-synonymous mutations that altered the amino acid sequence. Our study demonstrates that this commonly used antiviral can ‘supercharge’ viral evolution in immunocompromised patients, potentially generating new variants and prolonging the pandemic.
Main text
... These data highlight the risk of treating immunocompromised patients with error generating antivirals such as Molnupiravir. All of the individuals in our study remained persistently PCR positive post-treatment, although active monitoring for clearance was not undertaken by the institution. It is possible they were infectious in the hospital and in their communities, and onward transmission of these highly divergent viruses is likely. This commonly used class of antivirals has the capability to supercharge SARS-CoV-2 evolution, and uncontrolled use may generate new variants with a transmission advantage that prolongs the pandemic and makes other therapeutics less effective."
"This project was supported by an Australian Research Council Discovery Project Grant (DP190102020)."
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