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Artículo

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

Mizenina, Olga; Hsu, Mayla; Jean Pierre, Ninochka; Aravantinou, Meropi; Levendosky, Keith; Paglini, Maria GabrielaIcon ; Zydowsky, Thomas M.; Robbiani, Melissa; Fernández Romero, José A.
Fecha de publicación: 15/12/2017
Editorial: Springer
Revista: Drug Delivery and Translational Research
ISSN: 2190-3948
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Salud Ocupacional

Resumen

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.
Palabras clave: Antiviral , Hiv-1 , Microbicides , Nnrtis , Zinc
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/63812
URL: https://link.springer.com/article/10.1007/s13346-017-0421-4
DOI: https://dx.doi.org/10.1007/s13346-017-0421-4
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Articulos(INIMEC - CONICET)
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Citación
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
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