Oxidative DNA Damage by N4-hydroxycytidine, a Metabolite of the SARS-CoV-2 Antiviral Molnupiravir

التفاصيل البيبلوغرافية
العنوان: Oxidative DNA Damage by N4-hydroxycytidine, a Metabolite of the SARS-CoV-2 Antiviral Molnupiravir
المؤلفون: Hatasu Kobayashi, Yurie Mori, Sharif Ahmed, Yuichiro Hirao, Shinya Kato, Shosuke Kawanishi, Mariko Murata, Shinji Oikawa
المصدر: The Journal of Infectious Diseases. 227:1068-1072
بيانات النشر: Oxford University Press (OUP), 2022.
سنة النشر: 2022
مصطلحات موضوعية: Infectious Diseases, Immunology and Allergy
الوصف: Molnupiravir is an antiviral agent recently used for treating coronavirus disease 2019 (COVID-19). Here, we demonstrate that N4-hydroxycytidine (NHC), a molnupiravir metabolite, treated with cytidine deaminase (CDA) induced Cu(II)-mediated oxidative DNA damage in isolated DNA. A colorimetric assay revealed hydroxylamine generation from CDA-treated NHC. The site specificity of DNA damage also suggested involvement of hydroxylamine in the damage. Furthermore, Cu(I) and H2O2 play an important role in the DNA damage. We propose oxidative DNA damage via CDA-mediated metabolism as a possible mutagenic mechanism of NHC, highlighting the need for careful risk assessment of molnupiravir use in therapies for viral diseases, including COVID-19.
تدمد: 1537-6613
0022-1899
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::205727591eeb657bf60fb48a6a46772c
https://doi.org/10.1093/infdis/jiac477
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....205727591eeb657bf60fb48a6a46772c
قاعدة البيانات: OpenAIRE