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

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=1.5μM; YFV-17D EC50=0.83μM) and (iii) viral antigen production. Antiviral activity was also demonstrated in DENV subgenomic replicons (which do not encode the structural viral proteins) (EC50=2.3μM), 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.publisher: Elsevier articletitle: 3′,5′Di-O-trityluridine inhibits in vitro flavivirus replication journaltitle: Antiviral Research articlelink: http://dx.doi.org/10.1016/j.antiviral.2013.01.011 content_type: article copyright: Copyright © 2013 Elsevier B.V. All rights reserved.status: publishe