Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 297, Issue 1, Pages -Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1016/j.jbc.2021.100867
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Funding
- Spanish Ministry of Science and Innovation [PID2019-104176RB-I00/AEI/10.13039/50110001 1033]
- Fundacion Ramon Areces (Madrid, Spain)
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Molnupiravir can be incorporated into viral RNA and used as template for RNA synthesis, leading to error catastrophe in SARS-CoV-2.
Molnupiravir, a prodrug of the nucleoside derivative beta-D-N-4-hydroxycytidine (NHC), is currently in clinical trials for COVID-19 therapy. However, the biochemical mechanisms involved in molnupiravir-induced mutagenesis had not been explored. In a recent study, Gordon et al. demonstrated that NHC can be incorporated into viral RNA and subsequently extended and used as template for RNA-dependent RNA synthesis, proposing a mutagenesis model consistent with available virological evidence. Their study uncovers molecular mechanisms by which molnupiravir drives SARS-CoV-2 into error catastrophe.
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