Antiviral activity of the adenosine analogue BCX4430 against West Nile virus and tick-borne flaviviruses

• Published in: Antiviral research 2017-06, Vol.142, p.63-67
• Main Authors: Eyer, Luděk, Zouharová, Darina, Širmarová, Jana, Fojtíková, Martina, Štefánik, Michal, Haviernik, Jan, Nencka, Radim, de Clercq, Erik, Růžek, Daniel
• Format: Article
• Language: English
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine analogue; Animals; Antiviral activity; Antiviral Agents - pharmacology; BCX4430; Cell Line; Cell Survival - drug effects; Chlorocebus aethiops; Culicidae - virology; Cytotoxicity; Dose-Response Relationship, Drug; Encephalitis Viruses, Tick-Borne - drug effects; Encephalitis Viruses, Tick-Borne - pathogenicity; Encephalitis, Tick-Borne - transmission; Encephalitis, Tick-Borne - virology; Flavivirus; Flavivirus - drug effects; Nucleoside inhibitor; Purine Nucleosides - antagonists & inhibitors; Purine Nucleosides - chemistry; Swine; Tick-Borne Diseases; Ticks - virology; Vero Cells; Virus Replication - drug effects; West Nile virus - drug effects; West Nile virus - pathogenicity
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2017.03.012

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. [Display omitted] •BCX4430 showed varying degrees of antiviral activity against different tick-borne flaviviruses in cell culture.•BCX4430 strongly inhibited replication of West Nile virus in vitro.•BCX4430 exerted no or negligible cytotoxicity in porcine kidney stable or Vero cell cultures.•Comparable inhibition/cytotoxicity properties were observed for BCX4430 and its hydrochloride form.