%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Kaptein, S. J. F.
%A De Burghgraeve, T.
%A Froeyen, M.
%A Pastorino, B.
%A Alen, M. M. F.
%A Mondotte, J. A.
%A Herdewijn, P.
%A Jacobs, M.
%A de Lamballerie, Xavier
%A Schols, D.
%A Gamarnik, A. V.
%A Sztaricskai, F.
%A Neyts, J.
%T A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
%D 2010
%L PAR00006581
%G ENG
%J Antimicrobial Agents and Chemotherapy
%@ 0066-4804
%M ISI:000284158000044
%N 12
%P 5269-5280
%R 10.1128/aac.00686-10
%U https://www.documentation.ird.fr/hor/PAR00006581
%V 54
%W Horizon (IRD)
%X A doxorubicin derivate, SA-17, that carries a squaric acid amide ester moiety at the carbohydrate (alpha-L-daunosaminyl) group was identified as a selective inhibitor of in vitro dengue virus (DENV) serotype 2 replication (50% effective concentration [EC50] = 0.34 +/- 0.20 mu g/ml [0.52 +/- 0.31 mu M]). SA-17 is markedly less cytostatic than the parent compound, resulting in a selectivity index value of similar to 100. SA-17 also inhibits yellow fever virus 17D (YFV-17D) replication (EC50 = 3.1 +/- 1.0 mu g/ml [4.8 +/- 1.5 mu M]), although less efficiently than DENV replication, but proved inactive against a variety of enveloped and nonenveloped viruses. SA-17 inhibits in vitro flavivirus replication in a dose-dependent manner, as was assessed by virus yield reduction assays and quantification of viral RNA by means of real-time quantitative reverse transcriptase PCR (RT-qPCR) (similar to 2 to 3 log reduction). The anti-DENV activity was confirmed using a Renilla luciferase-expressing dengue reporter virus. Time-of-drug-addition studies revealed that SA-17 acts at the very early stages of the viral replication cycle (i.e., virus attachment and/or virus entry). This observation was corroborated by the observation that SA-17, unlike the nucleoside analogue ribavirin, does not inhibit the replication of DENV subgenomic replicons. Preincubation of high-titer stocks of DENV or YFV-17D with >= 5 mu g/ml SA-17 resulted in 100% inhibition of viral infectivity (>= 3 log reduction). SA-17, however, did not prove virucidal.
%$ 052