Antiviral activity of the adenosine analogue BCX4430 against West Nile virus and tick-borne flaviviruses
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
28336346
DOI
10.1016/j.antiviral.2017.03.012
PII: S0166-3542(17)30024-4
Knihovny.cz E-resources
- Keywords
- Adenosine analogue, Antiviral activity, BCX4430, Cytotoxicity, Flavivirus, Nucleoside inhibitor,
- MeSH
- Adenine analogs & derivatives MeSH
- Adenosine analogs & derivatives pharmacology MeSH
- Antiviral Agents pharmacology MeSH
- Cell Line MeSH
- Chlorocebus aethiops MeSH
- Culicidae virology MeSH
- Flavivirus drug effects MeSH
- Ticks virology MeSH
- Encephalitis, Tick-Borne transmission virology MeSH
- Tick-Borne Diseases MeSH
- Swine MeSH
- Purine Nucleosides antagonists & inhibitors chemistry MeSH
- Pyrrolidines MeSH
- Virus Replication drug effects MeSH
- Vero Cells MeSH
- Cell Survival drug effects MeSH
- West Nile virus drug effects pathogenicity MeSH
- Encephalitis Viruses, Tick-Borne drug effects pathogenicity MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adenine MeSH
- Adenosine MeSH
- Antiviral Agents MeSH
- galidesivir MeSH Browser
- Purine Nucleosides MeSH
- Pyrrolidines MeSH
There are currently no approved antiviral therapies against medically important human flaviviruses. The imino-C-nucleoside BCX4430 shows broad-spectrum antiviral activity against a wide range of RNA viruses. Here, we demonstrate that BCX4430 inhibits tick-borne species of the genus Flavivirus; however, the antiviral effect varies against individual species. Micro-molar BCX4430 levels inhibited tick-borne encephalitis virus (TBEV); while, approximately 3-8-fold higher concentrations were needed to inhibit louping ill virus and Kyasanur Forest disease virus. Moreover, the compound strongly inhibited in vitro replication of West Nile virus, a typical mosquito-transmitted flavivirus. Two chemical forms of the compound, i.e. BCX4430 and BCX4430 hydrochloride, were compared and both exerted similar inhibitory profiles in our in vitro antiviral assay systems and no or negligible cytotoxicity in porcine kidney stable and Vero cells. The obtained data indicate that, in addition to mosquito-borne flaviviruses, the compound has strong antiviral activity against members of the TBEV serocomplex.
Department of Virology Veterinary Research Institute Hudcova 70 CZ 62100 Brno Czech Republic
Rega Institute for Medical Research KU Leuven Minderbroedersstraat 10 B 3000 Leuven Belgium
References provided by Crossref.org
History of Arbovirus Research in the Czech Republic
Nucleoside analogs as a rich source of antiviral agents active against arthropod-borne flaviviruses
