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 embryotoxicity1-14. Multiple analyses have identified variants potentially created by molnupiravir15-19.

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

This Paper Molnupiravir All

DOI record: { "DOI": "10.1002/bmc.5996", "ISSN": [ "0269-3879", "1099-0801" ], "URL": "http://dx.doi.org/10.1002/bmc.5996", "abstract": "AbstractMolnupiravir (MO) is a pyrimidine nucleoside anti‐SARS‐CoV‐2 drug. 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). The current study indicated that the elevation of hepatic TLR may be an important reason for MO leading to the liver injury.", "alternative-id": [ "10.1002/bmc.5996" ], "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2024-06-16" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "2024-08-13" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 3, "value": "2024-08-23" } ], "author": [ { "affiliation": [ { "name": "Academician Workstation Jiangxi University of Chinese Medicine Nanchang China" }, { "name": "Department of Gastroenterology & Hepatology, Laboratory of Hepato‐intestinal Diseases and Metabolism, Frontiers Science Center for Disease‐Related Molecular Network, and State Key Laboratory of Respiratory 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