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ß-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells.
Zhou, Shuntai; Hill, Collin S; Sarkar, Sanjay; Tse, Longping V; Woodburn, Blaide M D; Schinazi, Raymond F; Sheahan, Timothy P; Baric, Ralph S; Heise, Mark T; Swanstrom, Ronald.
  • Zhou S; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Hill CS; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Sarkar S; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Tse LV; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Woodburn BMD; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Schinazi RF; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Sheahan TP; Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Heise MT; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  • Swanstrom R; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
J Infect Dis ; 224(3): 415-419, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1526165
Semantic information from SemMedBD (by NLM)
1. Virion LOCATION_OF 2019 novel coronavirus
Subject
Virion
Predicate
LOCATION_OF
Object
2019 novel coronavirus
2. Genome PART_OF RNA Viruses
Subject
Genome
Predicate
PART_OF
Object
RNA Viruses
3. Genome compared_with ribavirin
Subject
Genome
Predicate
compared_with
Object
ribavirin
4. Genome higher_than ribavirin
Subject
Genome
Predicate
higher_than
Object
ribavirin
5. Virion LOCATION_OF 2019 novel coronavirus
Subject
Virion
Predicate
LOCATION_OF
Object
2019 novel coronavirus
6. Genome PART_OF RNA Viruses
Subject
Genome
Predicate
PART_OF
Object
RNA Viruses
7. Genome compared_with ribavirin
Subject
Genome
Predicate
compared_with
Object
ribavirin
8. Genome higher_than ribavirin
Subject
Genome
Predicate
higher_than
Object
ribavirin
ABSTRACT
Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in genomes of RNA viruses during viral replication. ß-d-N4-hydroxycytidine (NHC, initial metabolite of molnupiravir) is >100-fold more active than ribavirin or favipiravir against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Antiviral Agents / Cytidine / SARS-CoV-2 / Mutagens Subject: Antiviral Agents / Cytidine / SARS-CoV-2 / Mutagens Language: English Journal: J Infect Dis Clinical aspect: Etiology Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Antiviral Agents / Cytidine / SARS-CoV-2 / Mutagens Subject: Antiviral Agents / Cytidine / SARS-CoV-2 / Mutagens Language: English Journal: J Infect Dis Clinical aspect: Etiology Year: 2021
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