Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1

Bacitracin and the membrane-impermeant thiol reagent 5,5’-dithiobis-2-nitrobenzoic acid (DTNB) are agents known to inhibit protein disulfide isomerase (PDI), a cell-surface protein critical in HIV-1 entry therefore they are fusion inhibitors (FI). Here we investigated the possibility that Bacitracin...

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Main Authors: Lara Villegas, Humberto Herman, Ixtepan Turrent, Liliana del Carmen, Garza Treviño, Elsa Nancy, Flores Teviño, Samantha M., Borkow, Gadi, Rodríguez Padilla, Cristina
Format: Article
Language:Spanish / Castilian
Published: 2011
Online Access:http://eprints.uanl.mx/15072/1/709.pdf
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author Lara Villegas, Humberto Herman
Ixtepan Turrent, Liliana del Carmen
Garza Treviño, Elsa Nancy
Flores Teviño, Samantha M.
Borkow, Gadi
Rodríguez Padilla, Cristina
author_facet Lara Villegas, Humberto Herman
Ixtepan Turrent, Liliana del Carmen
Garza Treviño, Elsa Nancy
Flores Teviño, Samantha M.
Borkow, Gadi
Rodríguez Padilla, Cristina
author_sort Lara Villegas, Humberto Herman
collection Repositorio Institucional
description Bacitracin and the membrane-impermeant thiol reagent 5,5’-dithiobis-2-nitrobenzoic acid (DTNB) are agents known to inhibit protein disulfide isomerase (PDI), a cell-surface protein critical in HIV-1 entry therefore they are fusion inhibitors (FI). Here we investigated the possibility that Bacitracin and or DTNB might have other antiviral activities besides FI. By means of residual activity assays, we found that both compounds showed antiviral activity only to viruses T-tropic HIV-1 strain. Cell-based fusion assays showed inhibition on HeLa-CD4-LTR-b-gal (CD4) and HL2/3 cells treated with Bacitracin, and DTNB with the latest compound we observed fusion inhibition on both cells but strikingly in HL2/3 cells (expressing Env) indicating a possible activity on both, the cell membrane and the viral envelope. A time-of-addition experiment showed that both compounds act on HIV entry inhibition but DTNB also acts at late stages of the viral cycle. Lastly, we also found evidence of long-lasting host cell protection in vitro by DTNB, an important pharmacodynamic parameter for a topical microbicide against virus infection, hours after the extracellular drug was removed; this protection was not rendered by Bacitracin. These drugs proved to be leading compounds for further studies against HIV showing antiviral characteristics of interest
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spelling eprints-150722024-12-11T15:26:46Z http://eprints.uanl.mx/15072/ Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1 Lara Villegas, Humberto Herman Ixtepan Turrent, Liliana del Carmen Garza Treviño, Elsa Nancy Flores Teviño, Samantha M. Borkow, Gadi Rodríguez Padilla, Cristina Bacitracin and the membrane-impermeant thiol reagent 5,5’-dithiobis-2-nitrobenzoic acid (DTNB) are agents known to inhibit protein disulfide isomerase (PDI), a cell-surface protein critical in HIV-1 entry therefore they are fusion inhibitors (FI). Here we investigated the possibility that Bacitracin and or DTNB might have other antiviral activities besides FI. By means of residual activity assays, we found that both compounds showed antiviral activity only to viruses T-tropic HIV-1 strain. Cell-based fusion assays showed inhibition on HeLa-CD4-LTR-b-gal (CD4) and HL2/3 cells treated with Bacitracin, and DTNB with the latest compound we observed fusion inhibition on both cells but strikingly in HL2/3 cells (expressing Env) indicating a possible activity on both, the cell membrane and the viral envelope. A time-of-addition experiment showed that both compounds act on HIV entry inhibition but DTNB also acts at late stages of the viral cycle. Lastly, we also found evidence of long-lasting host cell protection in vitro by DTNB, an important pharmacodynamic parameter for a topical microbicide against virus infection, hours after the extracellular drug was removed; this protection was not rendered by Bacitracin. These drugs proved to be leading compounds for further studies against HIV showing antiviral characteristics of interest 2011 Article PeerReviewed text es cc_by_nc_nd http://eprints.uanl.mx/15072/1/709.pdf http://eprints.uanl.mx/15072/1.haspreviewThumbnailVersion/709.pdf Lara Villegas, Humberto Herman y Ixtepan Turrent, Liliana del Carmen y Garza Treviño, Elsa Nancy y Flores Teviño, Samantha M. y Borkow, Gadi y Rodríguez Padilla, Cristina (2011) Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1. Virology journal, 8 (1). pp. 1-8. ISSN 1743-422X http://doi.org/10.1186/1743-422X-8-137 doi:10.1186/1743-422X-8-137
spellingShingle Lara Villegas, Humberto Herman
Ixtepan Turrent, Liliana del Carmen
Garza Treviño, Elsa Nancy
Flores Teviño, Samantha M.
Borkow, Gadi
Rodríguez Padilla, Cristina
Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1
title_full Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1
title_fullStr Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1
title_full_unstemmed Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1
title_short Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1
title_sort antiviral propierties of 5 5 dithiobis 2 nitrobenzoic acid and bacitracin against t tropic human immunodeficiency virus type 1
url http://eprints.uanl.mx/15072/1/709.pdf
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