Oxidative DNA Damage by N4-hydroxycytidine, a Metabolite of the SARS-CoV-2 Antiviral Molnupiravir
العنوان: | Oxidative DNA Damage by N4-hydroxycytidine, a Metabolite of the SARS-CoV-2 Antiviral Molnupiravir |
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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 |
تدمد: | 15376613 00221899 |
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