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An active metabolite of the anti-COVID-19 drug molnupiravir impairs mouse preimplantation embryos at clinically relevant concentrations

Marikawa et al., Reproductive Toxicology, doi:10.1016/j.reprotox.2023.108475
Sep 2023  
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Analysis of molnupiravir active metabolite N4-hydroxycytidine's effects on mouse preimplantation embryos in vitro, showing embryotoxicity at clinically relevant concentrations. The researchers found that N4-hydroxycytidine impaired blastocyst formation and caused cell death at concentrations below the therapeutic levels in humans. The adverse effects occurred when exposure happened after the 8-cell embryo stage and depended on nucleoside transporter activity. Transcriptomic analysis suggested N4-hydroxycytidine triggered the integrated stress response in embryos.
Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer Hadj Hassine, Huntsman, Marikawa, Swanstrom, Waters, Zhou, Zibat. Multiple analyses have identified variants potentially created by molnupiravir Fountain-Jones, Kosakovsky Pond, Sanderson, twitter.com.
Marikawa et al., 23 Sep 2023, peer-reviewed, 2 authors.
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