An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
32452412
DOI
10.1016/j.virol.2020.03.006
PII: S0042-6822(20)30059-3
Knihovny.cz E-zdroje
- Klíčová slova
- Molecular, Non-structural proteins, Simulation, TBEV, Viral inhibition,
- MeSH
- antivirové látky farmakologie MeSH
- inhibitory enzymů farmakologie MeSH
- klíšťata virologie MeSH
- klíšťová encefalitida virologie MeSH
- lidé MeSH
- replikace viru účinky léků MeSH
- RNA-dependentní RNA-polymerasa antagonisté a inhibitory genetika metabolismus MeSH
- virové proteiny antagonisté a inhibitory genetika metabolismus MeSH
- viry klíšťové encefalitidy účinky léků enzymologie genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antivirové látky MeSH
- inhibitory enzymů MeSH
- RNA-dependentní RNA-polymerasa MeSH
- virové proteiny MeSH
Tick-borne encephalitis virus (TBEV) is a medically important representative of the Flaviviridae family. The TBEV genome encodes a single polyprotein, which is co/post-translationally cleaved into three structural and seven non-structural proteins. Of the non-structural proteins, NS5, contains an RNA-dependent RNA polymerase (RdRp) domain that is highly conserved and is responsible for the genome replication. Screening for potential antivirals was done using a hybrid receptor and ligand-based pharmacophore search likely targeting the RdRp domain. For the identification of pharmacophores, a mixture of small probe molecules and nucleotide triphosphates were used. The ligand/receptor interaction screenings of structures from the ZINC database resulted in five compounds. Zinc 3677 and 7151 exhibited lower cytotoxicity and were tested for their antiviral effect against TBEV in vitro. Zinc 3677 inhibited TBEV at micromolar concentrations. The results indicate that Zinc 3677 represents a good target for structure-activity optimizations leading potentially to a discovery of effective TBEV antivirals.
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