Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/58978 |
Resumo: | Microbicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn’t cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women. |
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Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in womenMicrobicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn’t cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women.Financial support for this research was provided by the Fundação para a Ciência e a Tecnologia (FCT), Portugal (project VIH/SAU/0029/2011), part of the EDCTP2 program supported by the European Union. Inês Bártolo is supported by a post-doc fellowship (SFRH/BPD/76225/2011) from Fundação para a Ciência e Tecnologia (FCT), Portugal. Ana Rita Diniz is supported by a PhD grant (SFRH/BD/89140/2012) from Fundação para a Ciência e Tecnologia (FCT), Portugal. https://www.fct.pt/.PlosRepositório da Universidade de LisboaBártolo, InêsDiniz, Ana RitaBorrego, PedroFerreira, João PedroBronze, MRBarroso, HelenaPinto, RuiCardoso, CarlosPinto, João F.Ceña Diaz, RafaelBroncano, Pilar GarciaMuñoz-Fernandez, Maria AngelTaveira, Nuno2023-08-23T17:54:05Z20182023-02-03T14:18:26Z2018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/58978engBártolo I, Diniz AR, Borrego P, Ferreira JP, Bronze MR, Barroso H, et al. Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women. PLOS ONE [Internet]. 18 de abril de 2018;13(4):e0195744. Disponível em: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195744cv-prod-110844910.1371/journal.pone.01957442-s2.0-85045888895info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:03:33Zoai:repositorio.ul.pt:10451/58978Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:06:41.919390Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women |
title |
Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women |
spellingShingle |
Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women Bártolo, Inês |
title_short |
Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women |
title_full |
Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women |
title_fullStr |
Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women |
title_full_unstemmed |
Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women |
title_sort |
Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women |
author |
Bártolo, Inês |
author_facet |
Bártolo, Inês Diniz, Ana Rita Borrego, Pedro Ferreira, João Pedro Bronze, MR Barroso, Helena Pinto, Rui Cardoso, Carlos Pinto, João F. Ceña Diaz, Rafael Broncano, Pilar Garcia Muñoz-Fernandez, Maria Angel Taveira, Nuno |
author_role |
author |
author2 |
Diniz, Ana Rita Borrego, Pedro Ferreira, João Pedro Bronze, MR Barroso, Helena Pinto, Rui Cardoso, Carlos Pinto, João F. Ceña Diaz, Rafael Broncano, Pilar Garcia Muñoz-Fernandez, Maria Angel Taveira, Nuno |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Bártolo, Inês Diniz, Ana Rita Borrego, Pedro Ferreira, João Pedro Bronze, MR Barroso, Helena Pinto, Rui Cardoso, Carlos Pinto, João F. Ceña Diaz, Rafael Broncano, Pilar Garcia Muñoz-Fernandez, Maria Angel Taveira, Nuno |
description |
Microbicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn’t cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z 2023-08-23T17:54:05Z 2023-02-03T14:18:26Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/58978 |
url |
http://hdl.handle.net/10451/58978 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bártolo I, Diniz AR, Borrego P, Ferreira JP, Bronze MR, Barroso H, et al. Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women. PLOS ONE [Internet]. 18 de abril de 2018;13(4):e0195744. Disponível em: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195744 cv-prod-1108449 10.1371/journal.pone.0195744 2-s2.0-85045888895 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Plos |
publisher.none.fl_str_mv |
Plos |
dc.source.none.fl_str_mv |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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