@article{PAR00006581, title = {{A} derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro}, author = {{K}aptein, {S}. {J}. {F}. and {D}e {B}urghgraeve, {T}. and {F}roeyen, {M}. and {P}astorino, {B}. and {A}len, {M}. {M}. {F}. and {M}ondotte, {J}. {A}. and {H}erdewijn, {P}. and {J}acobs, {M}. and de {L}amballerie, {X}avier and {S}chols, {D}. and {G}amarnik, {A}. {V}. and {S}ztaricskai, {F}. and {N}eyts, {J}.}, editor = {}, language = {{ENG}}, abstract = {{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 [{EC}50] = 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 17{D} ({YFV}-17{D}) replication ({EC}50 = 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}-q{PCR}) (similar to 2 to 3 log reduction). {T}he anti-{DENV} activity was confirmed using a {R}enilla luciferase-expressing dengue reporter virus. {T}ime-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). {T}his observation was corroborated by the observation that {SA}-17, unlike the nucleoside analogue ribavirin, does not inhibit the replication of {DENV} subgenomic replicons. {P}reincubation of high-titer stocks of {DENV} or {YFV}-17{D} with >= 5 mu g/ml {SA}-17 resulted in 100% inhibition of viral infectivity (>= 3 log reduction). {SA}-17, however, did not prove virucidal.}, keywords = {}, booktitle = {}, journal = {{A}ntimicrobial {A}gents and {C}hemotherapy}, volume = {54}, numero = {12}, pages = {5269--5280}, ISSN = {0066-4804}, year = {2010}, DOI = {10.1128/aac.00686-10}, URL = {https://www.documentation.ird.fr/hor/{PAR}00006581}, }