Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis

Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mech...

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Veröffentlicht in:	Nature structural & molecular biology 2021-09, Vol.28 (9), p.740-746
Hauptverfasser:	Kabinger, Florian, Stiller, Carina, Schmitzová, Jana, Dienemann, Christian, Kokic, Goran, Hillen, Hauke S., Höbartner, Claudia, Cramer, Patrick
Format:	Artikel
Sprache:	eng
Schlagworte:	101/28 631/45/535/1258/1259 631/535/1258/1259 82 Animal models Animals Antiviral activity Antiviral agents Antiviral Agents - chemistry Antiviral Agents - metabolism Antiviral Agents - pharmacology Antiviral drugs Base Sequence Biochemistry Biological Microscopy Biomedical and Life Sciences Chemical properties Clinical trials Coronaviruses COVID-19 COVID-19 - prevention & control COVID-19 - virology COVID-19 Drug Treatment CTP Cytidine - analogs & derivatives Cytidine - chemistry Cytidine - metabolism Cytidine - pharmacology Cytidine triphosphate DNA-directed RNA polymerase Editing Evaluation Humans Hydroxylamines - chemistry Hydroxylamines - metabolism Hydroxylamines - pharmacology Life Sciences Membrane Biology Models, Molecular Molecular modelling Molecular Structure Mutagenesis Mutagenesis - drug effects Mutagenesis - genetics Mutation Mutation - drug effects Mutation - genetics Nucleic Acid Conformation Proofreading Protein Binding - drug effects Protein Conformation Protein Structure RNA polymerase RNA, Viral - chemistry RNA, Viral - genetics RNA, Viral - metabolism RNA-Dependent RNA Polymerase - chemistry RNA-Dependent RNA Polymerase - genetics RNA-Dependent RNA Polymerase - metabolism RNA-directed RNA polymerase SARS-CoV-2 - drug effects SARS-CoV-2 - genetics SARS-CoV-2 - physiology Severe acute respiratory syndrome coronavirus 2 Structural analysis Substrates Uridine Virus Replication - drug effects Virus Replication - genetics
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