Kaptein S. J. F., De Burghgraeve T., Froeyen M., Pastorino B., Alen M. M. F., Mondotte J. A., Herdewijn P., Jacobs M., de Lamballerie Xavier, Schols D., Gamarnik A. V., Sztaricskai F., Neyts J. (2010). A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro. Antimicrobial Agents and Chemotherapy, 54 (12), p. 5269-5280. ISSN 0066-4804.
Titre du document
A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
Année de publication
2010
Auteurs
Kaptein S. J. F., De Burghgraeve T., Froeyen M., Pastorino B., Alen M. M. F., Mondotte J. A., Herdewijn P., Jacobs M., de Lamballerie Xavier, Schols D., Gamarnik A. V., Sztaricskai F., Neyts J.
Source
Antimicrobial Agents and Chemotherapy, 2010,
54 (12), p. 5269-5280 ISSN 0066-4804
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.
Plan de classement
Entomologie médicale / Parasitologie / Virologie [052]
Identifiant IRD
PAR00006581
