Discussion of concerns with molnupiravir and the MOVe-OUT trial. Author notes that results showing bone marrow toxicity in dogs were mentioned in this preprint1, but removed from the journal version2. Some additional details were provided by the UK regulator:
“Reversible, dose-related bone marrow toxicity affecting all haematopoietic cell lines was observed in dogs at ≥17 mg/kg/day (0.4 times the human NHC exposure at the recommended human dose (RHD)).”3
This article can also be found at4.
3.
gov.uk, www.gov.uk/government/publications/regulatory-approval-of-lagevrio-molnupiravir/summary-of-product-characteristics-for-lagevrio.
5.
Tsai, T., Medico-legal integration of molnupiravir rapid deployment during the COVID-19 pandemic: Emergency use authorization, clinical evidence, and risk of viral mutagenesis, One Health, doi:10.1016/j.onehlt.2026.101621.
6.
Shen et al., Carboxylesterase Factors Influencing the Therapeutic Activity of Common Antiviral Medications Used for SARS-CoV-2 Infection, Pharmaceutics, doi:10.3390/pharmaceutics17070832.
7.
Bacigalupo et al., Unveiling patenting strategies of therapeutics and vaccines: evergreening in the context of COVID-19 pandemic, Frontiers in Medicine, doi:10.3389/fmed.2023.1287542.
8.
Kosakovsky Pond et al., Anti-COVID drug accelerates viral evolution, Nature, doi:10.1038/d41586-023-03248-3.
9.
Boretti, A., On the choice of Molnupiravir and Paxlovid as the only antivirals permitted for COVID-19 infection in Australia, Clinical and Experimental Medicine, doi:10.1007/s10238-023-01010-7.
10.
Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.
11.
Swanstrom et al., Lethal mutagenesis as an antiviral strategy, Science, doi:10.1126/science.abn0048.
12.
Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.
13.
Anonymous, Treating a Pandemic Respiratory Disease with a Mutagen is a Doomsday Scenario, Authorea, doi:10.22541/au.163854323.34557301/v1.
Goldstein et al., 6 Nov 2021, preprint, 1 author.