Author:

Keywords:

BCX4430, flavivirus, adenosine analogue, nucleoside inhibitor, antiviral activity, cytotoxicity, Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, Virology, Flavivirus, Adenosine analogue, Nucleoside inhibitor, Antiviral activity, Cytotoxicity, ENCEPHALITIS-VIRUS, NUCLEOSIDE INHIBITORS, MOUSE MODEL, ZIKA VIRUS, ARBOVIRUSES, VIRULENCE, CULTURE, FEVER, Adenine, Adenosine, Animals, Antiviral Agents, Cell Line, Cell Survival, Chlorocebus aethiops, Culicidae, Dose-Response Relationship, Drug, Encephalitis Viruses, Tick-Borne, Encephalitis, Tick-Borne, Purine Nucleosides, Pyrrolidines, Swine, Tick-Borne Diseases, Ticks, Vero Cells, Virus Replication, West Nile virus, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology and Pharmaceutical Sciences, 3107 Microbiology, 3207 Medical microbiology, 3214 Pharmacology and pharmaceutical sciences

Abstract:

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.