Detection of developmental toxicity of the anti-COVID-19 drug molnupiravir using gastruloid-based in vitro assays.
Molnupiravir, a COVID-19 drug, may pose developmental risks. Gastruloid models reveal it impairs embryo-like growth at clinically relevant doses, offering a faster, animal-free way to assess toxicity.
This study used gastruloids - 3D stem cell aggregates that mimic early embryonic development - to evaluate the developmental toxicity of molnupiravir's active metabolite, N4-hydroxycytidine (NHC). Experiments showed NHC significantly disrupted morphological progression and gene expression in mouse and human gastruloid models at concentrations comparable to human plasma levels. These findings demonstrate gastruloids can reliably detect the developmental risks of NHC, supporting their use as a non-animal tool to accelerate preclinical toxicity assessments of drugs like molnupiravir.