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Molnupiravir Active Metabolite–N4 hydroxycytidine causes Cytotoxicity to Mammalian Cells In Vitro

Pakotiprapha et al., ASPET 2024 Annual Meeting Abstract - Toxicology, doi:10.1124/jpet.212.937140
May 2024  
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In Vitro study showing cytotoxicity of N4-hydroxycytidine (NHC), the active metabolite of molnupiravir, at concentrations relevant to therapeutic doses of molnupiravir in COR-L23 and HepG2 cancer cell lines, and compared with cytotoxicity in normal HaCaT cells. NHC showed cytotoxicity in all three lines, with HaCaT cells showing lower IC50 values compared to both cancer cell lines at 3 and 5 days of treatment. The therapeutic dose of molnupiravir results in serum NHC concentrations close to the IC50 values obtained in this study.
Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer Chamod, Gruber, Hadj Hassine, Huntsman, Marikawa, Swanstrom, Waters, Zhou, Zibat. Multiple analyses have identified variants potentially created by molnupiravir Fountain-Jones, Kosakovsky Pond, Sanderson, twitter.com.
Pakotiprapha et al., 13 May 2024, peer-reviewed, 6 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperMolnupiravirAll
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