MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1

Autores
Mizenina, Olga; Hsu, Mayla; Jean Pierre, Ninochka; Aravantinou, Meropi; Levendosky, Keith; Paglini, Maria Gabriela; Zydowsky, Thomas M.; Robbiani, Melissa; Fernández Romero, José A.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs. Like other NNRTIs, MIV-150 has EC50 values in the subnanomolar to nanomolar range against wild type and NNRTI or RT-resistant HIVs. While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC50 values between 20 and 110 μM. The MIV-150/ZA combination had a potent and broad antiviral activity in primary cells. In vitro resistance selection studies revealed that previously described NNRTI-resistant mutations were selected by MIV-150. ZA-resistant virus retained susceptibility to MIV-150 (and other RTIs) and MIV-150-selected virus remained sensitive to ZA. Notably, resistant virus was not selected when cultured in the presence of both ZA and MIV-150. This underscores the potency and breadth of the MIV-150/ZA combination, supporting preclinical macaque studies and the advancement of MZC microbicides into clinical testing.
Fil: Mizenina, Olga. Center for Biomedical Research; Estados Unidos
Fil: Hsu, Mayla. Center for Biomedical Research; Estados Unidos
Fil: Jean Pierre, Ninochka. Center for Biomedical Research; Estados Unidos
Fil: Aravantinou, Meropi. Center for Biomedical Research; Estados Unidos
Fil: Levendosky, Keith. Center for Biomedical Research; Estados Unidos
Fil: Paglini, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología "Dr. J. M. Vanella"; Argentina
Fil: Zydowsky, Thomas M.. Center for Biomedical Research; Estados Unidos
Fil: Robbiani, Melissa. Center for Biomedical Research; Estados Unidos
Fil: Fernández Romero, José A.. Center for Biomedical Research; Estados Unidos. The City University of New York; Estados Unidos
Materia
Antiviral
Hiv-1
Microbicides
Nnrtis
Zinc
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/63812
Acceder
id CONICETDig_66982ab52de357dd0daaef8ad8c6742f
oai_identifier_str oai:ri.conicet.gov.ar:11336/63812
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1Mizenina, OlgaHsu, MaylaJean Pierre, NinochkaAravantinou, MeropiLevendosky, KeithPaglini, Maria GabrielaZydowsky, Thomas M.Robbiani, MelissaFernández Romero, José A.AntiviralHiv-1MicrobicidesNnrtisZinchttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs. Like other NNRTIs, MIV-150 has EC50 values in the subnanomolar to nanomolar range against wild type and NNRTI or RT-resistant HIVs. While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC50 values between 20 and 110 μM. The MIV-150/ZA combination had a potent and broad antiviral activity in primary cells. In vitro resistance selection studies revealed that previously described NNRTI-resistant mutations were selected by MIV-150. ZA-resistant virus retained susceptibility to MIV-150 (and other RTIs) and MIV-150-selected virus remained sensitive to ZA. Notably, resistant virus was not selected when cultured in the presence of both ZA and MIV-150. This underscores the potency and breadth of the MIV-150/ZA combination, supporting preclinical macaque studies and the advancement of MZC microbicides into clinical testing.Fil: Mizenina, Olga. Center for Biomedical Research; Estados UnidosFil: Hsu, Mayla. Center for Biomedical Research; Estados UnidosFil: Jean Pierre, Ninochka. Center for Biomedical Research; Estados UnidosFil: Aravantinou, Meropi. Center for Biomedical Research; Estados UnidosFil: Levendosky, Keith. Center for Biomedical Research; Estados UnidosFil: Paglini, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología "Dr. J. M. Vanella"; ArgentinaFil: Zydowsky, Thomas M.. Center for Biomedical Research; Estados UnidosFil: Robbiani, Melissa. Center for Biomedical Research; Estados UnidosFil: Fernández Romero, José A.. Center for Biomedical Research; Estados Unidos. The City University of New York; Estados UnidosSpringer2017-12-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/63812Mizenina, Olga; Hsu, Mayla; Jean Pierre, Ninochka; Aravantinou, Meropi; Levendosky, Keith; et al.; MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1; Springer; Drug Delivery and Translational Research; 7; 6; 15-12-2017; 859-8662190-3948CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s13346-017-0421-4info:eu-repo/semantics/altIdentifier/doi/10.1007/s13346-017-0421-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:21:05Zoai:ri.conicet.gov.ar:11336/63812instacron: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:34982025-10-15 14:21:05.696CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1
title MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1
spellingShingle MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1
Mizenina, Olga
Antiviral
Hiv-1
Microbicides
Nnrtis
Zinc
title_short MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1
title_full MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1
title_fullStr MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1
title_full_unstemmed MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1
title_sort MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1
dc.creator.none.fl_str_mv Mizenina, Olga
Hsu, Mayla
Jean Pierre, Ninochka
Aravantinou, Meropi
Levendosky, Keith
Paglini, Maria Gabriela
Zydowsky, Thomas M.
Robbiani, Melissa
Fernández Romero, José A.
author Mizenina, Olga
author_facet Mizenina, Olga
Hsu, Mayla
Jean Pierre, Ninochka
Aravantinou, Meropi
Levendosky, Keith
Paglini, Maria Gabriela
Zydowsky, Thomas M.
Robbiani, Melissa
Fernández Romero, José A.
author_role author
author2 Hsu, Mayla
Jean Pierre, Ninochka
Aravantinou, Meropi
Levendosky, Keith
Paglini, Maria Gabriela
Zydowsky, Thomas M.
Robbiani, Melissa
Fernández Romero, José A.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antiviral
Hiv-1
Microbicides
Nnrtis
Zinc
topic Antiviral
Hiv-1
Microbicides
Nnrtis
Zinc
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs. Like other NNRTIs, MIV-150 has EC50 values in the subnanomolar to nanomolar range against wild type and NNRTI or RT-resistant HIVs. While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC50 values between 20 and 110 μM. The MIV-150/ZA combination had a potent and broad antiviral activity in primary cells. In vitro resistance selection studies revealed that previously described NNRTI-resistant mutations were selected by MIV-150. ZA-resistant virus retained susceptibility to MIV-150 (and other RTIs) and MIV-150-selected virus remained sensitive to ZA. Notably, resistant virus was not selected when cultured in the presence of both ZA and MIV-150. This underscores the potency and breadth of the MIV-150/ZA combination, supporting preclinical macaque studies and the advancement of MZC microbicides into clinical testing.
Fil: Mizenina, Olga. Center for Biomedical Research; Estados Unidos
Fil: Hsu, Mayla. Center for Biomedical Research; Estados Unidos
Fil: Jean Pierre, Ninochka. Center for Biomedical Research; Estados Unidos
Fil: Aravantinou, Meropi. Center for Biomedical Research; Estados Unidos
Fil: Levendosky, Keith. Center for Biomedical Research; Estados Unidos
Fil: Paglini, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología "Dr. J. M. Vanella"; Argentina
Fil: Zydowsky, Thomas M.. Center for Biomedical Research; Estados Unidos
Fil: Robbiani, Melissa. Center for Biomedical Research; Estados Unidos
Fil: Fernández Romero, José A.. Center for Biomedical Research; Estados Unidos. The City University of New York; Estados Unidos
description We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs. Like other NNRTIs, MIV-150 has EC50 values in the subnanomolar to nanomolar range against wild type and NNRTI or RT-resistant HIVs. While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC50 values between 20 and 110 μM. The MIV-150/ZA combination had a potent and broad antiviral activity in primary cells. In vitro resistance selection studies revealed that previously described NNRTI-resistant mutations were selected by MIV-150. ZA-resistant virus retained susceptibility to MIV-150 (and other RTIs) and MIV-150-selected virus remained sensitive to ZA. Notably, resistant virus was not selected when cultured in the presence of both ZA and MIV-150. This underscores the potency and breadth of the MIV-150/ZA combination, supporting preclinical macaque studies and the advancement of MZC microbicides into clinical testing.
publishDate 2017
dc.date.none.fl_str_mv 2017-12-15
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/11336/63812
Mizenina, Olga; Hsu, Mayla; Jean Pierre, Ninochka; Aravantinou, Meropi; Levendosky, Keith; et al.; MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1; Springer; Drug Delivery and Translational Research; 7; 6; 15-12-2017; 859-866
2190-3948
CONICET Digital
CONICET
url http://hdl.handle.net/11336/63812
identifier_str_mv Mizenina, Olga; Hsu, Mayla; Jean Pierre, Ninochka; Aravantinou, Meropi; Levendosky, Keith; et al.; MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1; Springer; Drug Delivery and Translational Research; 7; 6; 15-12-2017; 859-866
2190-3948
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s13346-017-0421-4
info:eu-repo/semantics/altIdentifier/doi/10.1007/s13346-017-0421-4
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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 13.124843

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