Mass spectrometry‐based metabolomics reveals metabolism of molnupiravir may lead to metabolic disorders and hepatotoxicity

Chen et al., Biomedical Chromatography, doi:10.1002/bmc.5996

Aug 2024

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Analysis of molnupiravir induced liver injury. Molnupiravir treatment may disrupt metabolic homeostasis and cause liver injury by increasing levels of certain metabolites and activating inflammatory pathways.

Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-10. Multiple analyses have identified variants potentially created by molnupiravir11-15.

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Chen et al., 23 Aug 2024, peer-reviewed, 8 authors.

This Paper Molnupiravir All

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MO treatment could cause mild liver injury. However, the underlying ' 'mechanism of MO‐induced liver injury and the metabolic pathway of MO in vivo are unclear. In ' 'this study, metabolomics analysis and molecular biology methods were used to explore these ' 'issues. Through metabolomics analysis, it was found that the homeostasis of pyrimidine, ' 'purine, lysophosphatidylcholine (LPC), and amino acids in mice was destroyed after MO ' 'treatment. A total of 80 changed metabolites were detected. Among these changed metabolites, ' '4‐ethylphenyl sulfate, dihydrouracil, and LPC 20:0 was related to the elevation of alkaline ' 'phosphatase (ALP), interleukin‐6 (IL6), and nuclear factor kappa‐B (NF‐κB). The levels of ' '4‐ethylphenyl sulfate, dihydrouracil, and LPC 20:0 in plasma were positively correlated with ' 'their levels in the liver, suggesting that these metabolites were associated with MO‐induced ' 'liver injury. MO treatment could increase NHC and cytidine levels, activate cytidine ' 'deaminase (CDA), and increase LPC levels. CDA and LPC could increase the mRNA expression ' 'level of toll‐like receptor (TLR). 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