An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.

Autores
De Burghgraeve, Tine; Kaptein, Suzanne J. F.; Ayala Nunez, Nilda V.; Mondotte, Juan Alberto; Pastorino, Boris; Printsevskaya, Svetlana S.; de Lamballerie, Xavier; Jacobs, Michael; Preobrazhenskaya, Maria; Gamarnik, Andrea Vanesa; Smit, Jolanda M.; Neyts, Johan
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We 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. Virus infection was completely inhibited at concentrations that had no adverse effect on the host cells. These findings were corroborated by quantification of viral RNA levels in culture supernatant. Antiviral activity was also observed against other flaviviruses such as the yellow fever virus and the tick-borne encephalitis virus (TBEV). In particular, potent antiviral activity was observed against TBEV. Time-of-drug-addition experiments indicated that LCTA-949 inhibits an early stage in the DENV replication cycle; however, a virucidal effect was excluded. This observation was corroborated by the fact that LCTA-949 lacks activity on DENV subgenomic replicon (that does not encode structural proteins) replication. Using a microsopy-based binding and fusion assay employing DiD-labeled viruses, it was shown that LCTA-949 targets the early stage (binding/entry) of the infection. Moreover, LCTA-949 efficiently inhibits infectivity of DENV particles pre-opsonized with antibodies, thus potentially also inhibiting antibody-dependent enhancement (ADE). In 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.
Fil: De Burghgraeve, Tine. Katholikie Universiteit Leuven; Bélgica
Fil: Kaptein, Suzanne J. F.. Katholikie Universiteit Leuven; Bélgica
Fil: Ayala Nunez, Nilda V.. University of Groningen; Países Bajos
Fil: Mondotte, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Pastorino, Boris. Université de la Méditerranée; Francia
Fil: Printsevskaya, Svetlana S.. Russian Academy of Medical Sciences; Rusia
Fil: de Lamballerie, Xavier. Université de la Méditerranée; Francia
Fil: Jacobs, Michael. Royal Free & University College Medical School; Reino Unido
Fil: Preobrazhenskaya, Maria. Russian Academy of Medical Sciences; Rusia
Fil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Smit, Jolanda M.. University of Groningen; Países Bajos
Fil: Neyts, Johan. Katholikie Universiteit Leuven; Bélgica
Materia
antivirals
dengue virus
viral inhibition
flavivirus
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/20752
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/20752
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.De Burghgraeve, TineKaptein, Suzanne J. F.Ayala Nunez, Nilda V.Mondotte, Juan AlbertoPastorino, BorisPrintsevskaya, Svetlana S.de Lamballerie, XavierJacobs, MichaelPreobrazhenskaya, MariaGamarnik, Andrea VanesaSmit, Jolanda M.Neyts, Johanantiviralsdengue virusviral inhibitionflavivirushttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We 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. Virus infection was completely inhibited at concentrations that had no adverse effect on the host cells. These findings were corroborated by quantification of viral RNA levels in culture supernatant. Antiviral activity was also observed against other flaviviruses such as the yellow fever virus and the tick-borne encephalitis virus (TBEV). In particular, potent antiviral activity was observed against TBEV. Time-of-drug-addition experiments indicated that LCTA-949 inhibits an early stage in the DENV replication cycle; however, a virucidal effect was excluded. This observation was corroborated by the fact that LCTA-949 lacks activity on DENV subgenomic replicon (that does not encode structural proteins) replication. Using a microsopy-based binding and fusion assay employing DiD-labeled viruses, it was shown that LCTA-949 targets the early stage (binding/entry) of the infection. Moreover, LCTA-949 efficiently inhibits infectivity of DENV particles pre-opsonized with antibodies, thus potentially also inhibiting antibody-dependent enhancement (ADE). In 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.Fil: De Burghgraeve, Tine. Katholikie Universiteit Leuven; BélgicaFil: Kaptein, Suzanne J. F.. Katholikie Universiteit Leuven; BélgicaFil: Ayala Nunez, Nilda V.. University of Groningen; Países BajosFil: Mondotte, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Pastorino, Boris. Université de la Méditerranée; FranciaFil: Printsevskaya, Svetlana S.. Russian Academy of Medical Sciences; RusiaFil: de Lamballerie, Xavier. Université de la Méditerranée; FranciaFil: Jacobs, Michael. Royal Free & University College Medical School; Reino UnidoFil: Preobrazhenskaya, Maria. Russian Academy of Medical Sciences; RusiaFil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Smit, Jolanda M.. University of Groningen; Países BajosFil: Neyts, Johan. Katholikie Universiteit Leuven; BélgicaPublic Library Of Science2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/20752De Burghgraeve, Tine; Kaptein, Suzanne J. F.; Ayala Nunez, Nilda V.; Mondotte, Juan Alberto; Pastorino, Boris; et al.; An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.; Public Library Of Science; Plos One; 7; 5; 5-2012; e372441932-62031932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037244info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0037244info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:41:53Zoai:ri.conicet.gov.ar:11336/20752instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:41:53.845CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
title An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
spellingShingle An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
De Burghgraeve, Tine
antivirals
dengue virus
viral inhibition
flavivirus
title_short An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
title_full An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
title_fullStr An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
title_full_unstemmed An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
title_sort An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.
dc.creator.none.fl_str_mv De Burghgraeve, Tine
Kaptein, Suzanne J. F.
Ayala Nunez, Nilda V.
Mondotte, Juan Alberto
Pastorino, Boris
Printsevskaya, Svetlana S.
de Lamballerie, Xavier
Jacobs, Michael
Preobrazhenskaya, Maria
Gamarnik, Andrea Vanesa
Smit, Jolanda M.
Neyts, Johan
author De Burghgraeve, Tine
author_facet De Burghgraeve, Tine
Kaptein, Suzanne J. F.
Ayala Nunez, Nilda V.
Mondotte, Juan Alberto
Pastorino, Boris
Printsevskaya, Svetlana S.
de Lamballerie, Xavier
Jacobs, Michael
Preobrazhenskaya, Maria
Gamarnik, Andrea Vanesa
Smit, Jolanda M.
Neyts, Johan
author_role author
author2 Kaptein, Suzanne J. F.
Ayala Nunez, Nilda V.
Mondotte, Juan Alberto
Pastorino, Boris
Printsevskaya, Svetlana S.
de Lamballerie, Xavier
Jacobs, Michael
Preobrazhenskaya, Maria
Gamarnik, Andrea Vanesa
Smit, Jolanda M.
Neyts, Johan
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv antivirals
dengue virus
viral inhibition
flavivirus
topic antivirals
dengue virus
viral inhibition
flavivirus
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We 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. Virus infection was completely inhibited at concentrations that had no adverse effect on the host cells. These findings were corroborated by quantification of viral RNA levels in culture supernatant. Antiviral activity was also observed against other flaviviruses such as the yellow fever virus and the tick-borne encephalitis virus (TBEV). In particular, potent antiviral activity was observed against TBEV. Time-of-drug-addition experiments indicated that LCTA-949 inhibits an early stage in the DENV replication cycle; however, a virucidal effect was excluded. This observation was corroborated by the fact that LCTA-949 lacks activity on DENV subgenomic replicon (that does not encode structural proteins) replication. Using a microsopy-based binding and fusion assay employing DiD-labeled viruses, it was shown that LCTA-949 targets the early stage (binding/entry) of the infection. Moreover, LCTA-949 efficiently inhibits infectivity of DENV particles pre-opsonized with antibodies, thus potentially also inhibiting antibody-dependent enhancement (ADE). In 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.
Fil: De Burghgraeve, Tine. Katholikie Universiteit Leuven; Bélgica
Fil: Kaptein, Suzanne J. F.. Katholikie Universiteit Leuven; Bélgica
Fil: Ayala Nunez, Nilda V.. University of Groningen; Países Bajos
Fil: Mondotte, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Pastorino, Boris. Université de la Méditerranée; Francia
Fil: Printsevskaya, Svetlana S.. Russian Academy of Medical Sciences; Rusia
Fil: de Lamballerie, Xavier. Université de la Méditerranée; Francia
Fil: Jacobs, Michael. Royal Free & University College Medical School; Reino Unido
Fil: Preobrazhenskaya, Maria. Russian Academy of Medical Sciences; Rusia
Fil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Smit, Jolanda M.. University of Groningen; Países Bajos
Fil: Neyts, Johan. Katholikie Universiteit Leuven; Bélgica
description There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We 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. Virus infection was completely inhibited at concentrations that had no adverse effect on the host cells. These findings were corroborated by quantification of viral RNA levels in culture supernatant. Antiviral activity was also observed against other flaviviruses such as the yellow fever virus and the tick-borne encephalitis virus (TBEV). In particular, potent antiviral activity was observed against TBEV. Time-of-drug-addition experiments indicated that LCTA-949 inhibits an early stage in the DENV replication cycle; however, a virucidal effect was excluded. This observation was corroborated by the fact that LCTA-949 lacks activity on DENV subgenomic replicon (that does not encode structural proteins) replication. Using a microsopy-based binding and fusion assay employing DiD-labeled viruses, it was shown that LCTA-949 targets the early stage (binding/entry) of the infection. Moreover, LCTA-949 efficiently inhibits infectivity of DENV particles pre-opsonized with antibodies, thus potentially also inhibiting antibody-dependent enhancement (ADE). In 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.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/20752
De Burghgraeve, Tine; Kaptein, Suzanne J. F.; Ayala Nunez, Nilda V.; Mondotte, Juan Alberto; Pastorino, Boris; et al.; An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.; Public Library Of Science; Plos One; 7; 5; 5-2012; e37244
1932-6203
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/20752
identifier_str_mv De Burghgraeve, Tine; Kaptein, Suzanne J. F.; Ayala Nunez, Nilda V.; Mondotte, Juan Alberto; Pastorino, Boris; et al.; An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro.; Public Library Of Science; Plos One; 7; 5; 5-2012; e37244
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037244
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0037244
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library Of Science
publisher.none.fl_str_mv Public Library Of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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