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

0479053 - BC 2018 RIV NL eng J - Článek v odborném periodiku
Eyer, Luděk - Zouharová, D. - Širmarová, J. - Fojtiková, M. - Štefánik, M. - Haviernik, J. - Nencka, Radim - De Clercq, E. - Růžek, Daniel
Antiviral activity of the adenosine analogue BCX4430 against West Nile virus and tick-borne flaviviruses.
Antiviral Research. Roč. 142, JUN (2017), s. 63-67. ISSN 0166-3542. E-ISSN 1872-9096
Grant CEP: GA MZd(CZ) NV16-34238A; GA ČR(CZ) GA16-20054S
Institucionální podpora: RVO:60077344 ; RVO:61388963
Klíčová slova: BCX4430 * Flavivirus * adenosine analogue * nucleoside inhibitor * antiviral activity * cytotoxicity
Obor OECD: Virology
Impakt faktor: 4.307, rok: 2017

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. (C) 2017 Elsevier B.V. All rights reserved.
Trvalý link: http://hdl.handle.net/11104/0275078