An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32452412
DOI
10.1016/j.virol.2020.03.006
PII: S0042-6822(20)30059-3
Knihovny.cz E-resources
- Keywords
- Molecular, Non-structural proteins, Simulation, TBEV, Viral inhibition,
- MeSH
- Antiviral Agents pharmacology MeSH
- Enzyme Inhibitors pharmacology MeSH
- Ticks virology MeSH
- Encephalitis, Tick-Borne virology MeSH
- Humans MeSH
- Virus Replication drug effects MeSH
- RNA-Dependent RNA Polymerase antagonists & inhibitors genetics metabolism MeSH
- Viral Proteins antagonists & inhibitors genetics metabolism MeSH
- Encephalitis Viruses, Tick-Borne drug effects enzymology genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antiviral Agents MeSH
- Enzyme Inhibitors MeSH
- RNA-Dependent RNA Polymerase MeSH
- Viral Proteins 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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