3',5'Di-O-trityluridine inhibits in vitro flavivirus replication.

Abstract:

:The dengue fever virus (DENV) and the yellow fever virus (YFV) are members of the genus flavivirus in the family Flaviviridae. An estimated 50-100 million cases of DENV infections occur each year and approximately half a million patients require hospitalization. There is no vaccine or effective antiviral treatment available. There is an urgent need for potent and safe inhibitors of DENV replication; ideally such compounds should have broad-spectrum activity against flaviviruses. We here report on the in vitro activity of 3',5'di-O-trityluridine on flavivirus replication. The compound results in a dose-dependent inhibition of (i) DENV- and YFV-induced cytopathic effect (CPE) (EC₅₀ values in the low micromolar range for the 4 DENV serotypes), (ii) RNA replication (DENV-2 EC₅₀=1.5 μM; YFV-17D EC₅₀=0.83 μM) and (iii) viral antigen production. Antiviral activity was also demonstrated in DENV subgenomic replicons (which do not encode the structural viral proteins) (EC₅₀=2.3 μM), indicating that the compound inhibits intracellular events of the viral replication cycle. Preliminary data indicate that the molecule may inhibit the viral RNA-dependent RNA polymerase.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

De Burghgraeve T,Selisko B,Kaptein S,Chatelain G,Leyssen P,Debing Y,Jacobs M,Van Aerschot A,Canard B,Neyts J

doi

10.1016/j.antiviral.2013.01.011

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

242-7

issue

2

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(13)00053-3

journal_volume

98

pub_type

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