Antiviral Activity of 7-Substituted 7-Deazapurine Ribonucleosides, Monophosphate Prodrugs, and Triphoshates against Emerging RNA Viruses
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- Klíčová slova
- 7-deazapurine ribonucleosides, RNA viruses, antiviral activity, monophosphate prodrugs, triphoshates,
- MeSH
- antivirové látky farmakologie MeSH
- COVID-19 virologie MeSH
- farmakoterapie COVID-19 MeSH
- fosfáty farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- prekurzory léčiv farmakologie MeSH
- purinové nukleosidy MeSH
- puriny farmakologie MeSH
- ribonukleosidy farmakologie MeSH
- RNA-dependentní RNA-polymerasa metabolismus MeSH
- RNA-viry účinky léků MeSH
- SARS-CoV-2 účinky léků MeSH
- virus dengue účinky léků MeSH
- virus západního Nilu účinky léků MeSH
- virus zika účinky léků MeSH
- viry klíšťové encefalitidy účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 7-deazapurine MeSH Prohlížeč
- antivirové látky MeSH
- fosfáty MeSH
- prekurzory léčiv MeSH
- purinové nukleosidy MeSH
- puriny MeSH
- ribonukleosidy MeSH
- RNA-dependentní RNA-polymerasa 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.
Citace poskytuje Crossref.org
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