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.
- MeSH
- adenosin analogy a deriváty farmakologie MeSH
- antivirové látky farmakologie MeSH
- buněčné linie MeSH
- Cercopithecus aethiops MeSH
- Culicidae virologie MeSH
- Flavivirus účinky léků MeSH
- klíšťata virologie MeSH
- klíšťová encefalitida přenos virologie MeSH
- nemoci přenášené klíšťaty MeSH
- prasata MeSH
- purinové nukleosidy antagonisté a inhibitory chemie MeSH
- replikace viru účinky léků MeSH
- Vero buňky MeSH
- viabilita buněk účinky léků MeSH
- virus západního Nilu účinky léků patogenita MeSH
- viry klíšťové encefalitidy účinky léků patogenita MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH