@article{PAR00009046, title = {{A}n analogue of the antibiotic {T}eicoplanin prevents {F}lavivirus entry in vitro}, author = {{D}e {B}urghgraeve, {T}. and {K}aptein, {S}. {J}. {F}. and {A}yala-{N}unez, {N}. {V}. and {M}ondotte, {J}. {A}. and {P}astorino, {B}. and {P}rintsevskaya, {S}. {S}. and de {L}amballerie, {X}avier and {J}acobs, {M}. and {P}reobrazhenskaya, {M}. and {G}amarnik, {A}. {V}. and {S}mit, {J}. {M}. and {N}eyts, {J}.}, editor = {}, language = {{ENG}}, abstract = {{T}here is an urgent need for potent inhibitors of dengue virus ({DENV}) replication for the treatment and/or prophylaxis of infections with this virus. {W}e here report on an aglycon analogue of the antibiotic teicoplanin (code name {LCTA}-949) that inhibits {DENV}-induced cytopathic effect ({CPE}) in a dose-dependent manner. {V}irus infection was completely inhibited at concentrations that had no adverse effect on the host cells. {T}hese findings were corroborated by quantification of viral {RNA} levels in culture supernatant. {A}ntiviral activity was also observed against other flaviviruses such as the yellow fever virus and the tick-borne encephalitis virus ({TBEV}). {I}n particular, potent antiviral activity was observed against {TBEV}. {T}ime-of-drug-addition experiments indicated that {LCTA}-949 inhibits an early stage in the {DENV} replication cycle; however, a virucidal effect was excluded. {T}his observation was corroborated by the fact that {LCTA}-949 lacks activity on {DENV} subgenomic replicon (that does not encode structural proteins) replication. {U}sing a microsopy-based binding and fusion assay employing {D}i{D}-labeled viruses, it was shown that {LCTA}-949 targets the early stage (binding/entry) of the infection. {M}oreover, {LCTA}-949 efficiently inhibits infectivity of {DENV} particles pre-opsonized with antibodies, thus potentially also inhibiting antibody-dependent enhancement ({ADE}). {I}n conclusion, {LCTA}-949 exerts in vitro activity against several flaviviruses and does so (as shown for {DENV}) by interfering with an early step in the viral replication cycle.}, keywords = {}, booktitle = {}, journal = {{P}los {O}ne}, volume = {7}, numero = {5}, pages = {e37244}, ISSN = {1932-6203}, year = {2012}, DOI = {10.1371/journal.pone.0037244}, URL = {https://www.documentation.ird.fr/hor/{PAR}00009046}, }