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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 cancer1-9. Multiple analyses have identified variants potentially created by molnupiravir10-13.
Marikawa et al., 23 Sep 2023, peer-reviewed, 2 authors.
This PaperMolnupiravirAll
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