Antiviral Activity of 7-Substituted 7-Deazapurine Ribonucleosides, Monophosphate Prodrugs, and Triphoshates against Emerging RNA Viruses
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- 7-deazapurine ribonucleosides, RNA viruses, antiviral activity, monophosphate prodrugs, triphoshates,
- MeSH
- Antiviral Agents pharmacology MeSH
- COVID-19 virology MeSH
- COVID-19 Drug Treatment MeSH
- Phosphates pharmacology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Prodrugs pharmacology MeSH
- Purine Nucleosides MeSH
- Purines pharmacology MeSH
- Ribonucleosides pharmacology MeSH
- RNA-Dependent RNA Polymerase metabolism MeSH
- RNA Viruses drug effects MeSH
- SARS-CoV-2 drug effects MeSH
- Dengue Virus drug effects MeSH
- West Nile virus drug effects MeSH
- Zika Virus drug effects MeSH
- Encephalitis Viruses, Tick-Borne drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 7-deazapurine MeSH Browser
- Antiviral Agents MeSH
- Phosphates MeSH
- Prodrugs MeSH
- Purine Nucleosides MeSH
- Purines MeSH
- Ribonucleosides MeSH
- RNA-Dependent RNA Polymerase MeSH
A series of 7-deazaadenine ribonucleosides bearing alkyl, alkenyl, alkynyl, aryl, or hetaryl groups at position 7 as well as their 5'-O-triphosphates and two types of monophosphate prodrugs (phosphoramidates and S-acylthioethanol esters) were prepared and tested for antiviral activity against selected RNA viruses (Dengue, Zika, tick-borne encephalitis, West Nile, and SARS-CoV-2). The modified triphosphates inhibited the viral RNA-dependent RNA polymerases at micromolar concentrations through the incorporation of the modified nucleotide and stopping a further extension of the RNA chain. 7-Deazaadenosine nucleosides bearing ethynyl or small hetaryl groups at position 7 showed (sub)micromolar antiviral activities but significant cytotoxicity, whereas the nucleosides bearing bulkier heterocycles were still active but less toxic. Unexpectedly, the monophosphate prodrugs were similarly or less active than the corresponding nucleosides in the in vitro antiviral assays, although the bis(S-acylthioethanol) prodrug 14h was transported to the Huh7 cells and efficiently released the nucleoside monophosphate.
References provided by Crossref.org
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