West Nile virus (WNV) is a medically important emerging arbovirus causing serious neuroinfections in humans and against which no approved antiviral therapy is currently available. In this study, we demonstrate that 2'-C-methyl- or 4'-azido-modified nucleosides are highly effective inhibitors of WNV replication, showing nanomolar or low micromolar anti-WNV activity and negligible cytotoxicity in cell culture. One representative of C2'-methylated nucleosides, 7-deaza-2'-C-methyladenosine, significantly protected WNV-infected mice from disease progression and mortality. Twice daily treatment at 25 mg/kg starting at the time of infection resulted in 100% survival of the mice. This compound was highly effective, even if the treatment was initiated 3 days postinfection, at the time of a peak of viremia, which resulted in a 90% survival rate. However, the antiviral effect of 7-deaza-2'-C-methyladenosine was absent or negligible when the treatment was started 8 days postinfection (i.e., at the time of extensive brain infection). The 4'-azido moiety appears to be another important determinant for highly efficient inhibition of WNV replication in vitro However, the strong anti-WNV effect of 4'-azidocytidine and 4'-azido-aracytidine was cell type dependent and observed predominantly in porcine kidney stable (PS) cells. The effect was much less pronounced in Vero cells. Our results indicate that 2'-C-methylated or 4'-azidated nucleosides merit further investigation as potential therapeutic agents for treating WNV infections as well as infections caused by other medically important flaviviruses.

• Klíčová slova
• West Nile virus, antiviral agents, flavivirus, nucleoside analogs,
• MeSH
• antivirové látky terapeutické užití   MeSH
• buněčné linie MeSH
• Cercopithecus aethiops MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• prasata MeSH
• progrese nemoci MeSH
• replikace viru účinky léků   MeSH
• RNA-dependentní RNA-polymerasa antagonisté a inhibitory   MeSH
• tubercidin analogy a deriváty   terapeutické užití   MeSH
• Vero buňky MeSH
• viremie farmakoterapie   MeSH
• virus západního Nilu účinky léků   genetika   MeSH
• západonilská horečka farmakoterapie   patologie   virologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7-deaza-2'-C-methyladenosine MeSH Prohlížeč
• antivirové látky MeSH
• RNA-dependentní RNA-polymerasa MeSH
• tubercidin MeSH

Six kea (Nestor notabilis) in human care, naturally infected with West Nile virus (WNV) lineage 2 in Vienna, Austria, in 2008, developed mild to fatal neurological signs. WNV RNA persisted and the virus evolved in the birds' brains, as demonstrated by (phylo)genetic analyses of the complete viral genomes detected in kea euthanized between 2009 and 2014. WNV antibodies persisted in the birds, too. Chronic WNV infection in the brain might contribute to the circulation of the virus through oral transmission to predatory birds.

• Klíčová slova
• Austria, Kea, Lineage 2, Nestor notabilis, Persistent infection, Psittaciformes, WNV, West Nile virus,
• MeSH
• chronická nemoc MeSH
• epidemický výskyt choroby MeSH
• fylogeneze MeSH
• genom virový genetika   MeSH
• mozek patologie   virologie   MeSH
• nemoci ptáků patologie   virologie   MeSH
• papouškovití virologie   MeSH
• virus západního Nilu klasifikace   izolace a purifikace   fyziologie   MeSH
• západonilská horečka patologie   veterinární   virologie   MeSH
• zvířata v ZOO MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Rakousko MeSH