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

Jessada Pakotiprapha; Krittin Tangjittham; Tanaboon Rimdusit; Onmanee Prajuabjinda; Saovapak Poomirat; Sutheera Sangsiri

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

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.

Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-15. Multiple analyses have identified variants potentially created by molnupiravir16-20.

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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.

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