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Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo
Herpes simplex virus type 2 (HSV-2) is the causative pathogen of genital herpes and is closely associated with the occurrence of cervical cancer and human immunodeficiency virus (HIV) infection. The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside anal...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869512/ https://www.ncbi.nlm.nih.gov/pubmed/29522484 http://dx.doi.org/10.3390/v10030119 |
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author | Dai, Wenwen Wu, Yu Bi, Jinpeng Wang, Shuai Li, Fang Kong, Wei Barbier, Julien Cintrat, Jean-Christophe Gao, Feng Gillet, Daniel Su, Weiheng Jiang, Chunlai |
author_facet | Dai, Wenwen Wu, Yu Bi, Jinpeng Wang, Shuai Li, Fang Kong, Wei Barbier, Julien Cintrat, Jean-Christophe Gao, Feng Gillet, Daniel Su, Weiheng Jiang, Chunlai |
author_sort | Dai, Wenwen |
collection | PubMed |
description | Herpes simplex virus type 2 (HSV-2) is the causative pathogen of genital herpes and is closely associated with the occurrence of cervical cancer and human immunodeficiency virus (HIV) infection. The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside analogs emphasize the urgent need for alternative antivirals against HSV-2. Recently, ABMA [1-adamantyl (5-bromo-2-methoxybenzyl) amine] has been demonstrated to be an inhibitor of several pathogens exploiting host-vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that ABMA inhibited HSV-2-induced cytopathic effects and plaque formation with 50% effective concentrations of 1.66 and 1.08 μM, respectively. We also preliminarily demonstrated in a time of compound addition assay that ABMA exerted a dual antiviral mechanism by impairing virus entry, as well as the late stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that ABMA protected BALB/c mice from intravaginal HSV-2 challenge with an improved survival rate of 50% at 5 mg/kg (8.33% for the untreated virus infected control). Consequently, our study has identified ABMA as an effective inhibitor of HSV-2, both in vitro and in vivo, for the first time and presents an alternative to nucleoside analogs for HSV-2 infection treatment. |
format | Online Article Text |
id | pubmed-5869512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58695122018-03-28 Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo Dai, Wenwen Wu, Yu Bi, Jinpeng Wang, Shuai Li, Fang Kong, Wei Barbier, Julien Cintrat, Jean-Christophe Gao, Feng Gillet, Daniel Su, Weiheng Jiang, Chunlai Viruses Article Herpes simplex virus type 2 (HSV-2) is the causative pathogen of genital herpes and is closely associated with the occurrence of cervical cancer and human immunodeficiency virus (HIV) infection. The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside analogs emphasize the urgent need for alternative antivirals against HSV-2. Recently, ABMA [1-adamantyl (5-bromo-2-methoxybenzyl) amine] has been demonstrated to be an inhibitor of several pathogens exploiting host-vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that ABMA inhibited HSV-2-induced cytopathic effects and plaque formation with 50% effective concentrations of 1.66 and 1.08 μM, respectively. We also preliminarily demonstrated in a time of compound addition assay that ABMA exerted a dual antiviral mechanism by impairing virus entry, as well as the late stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that ABMA protected BALB/c mice from intravaginal HSV-2 challenge with an improved survival rate of 50% at 5 mg/kg (8.33% for the untreated virus infected control). Consequently, our study has identified ABMA as an effective inhibitor of HSV-2, both in vitro and in vivo, for the first time and presents an alternative to nucleoside analogs for HSV-2 infection treatment. MDPI 2018-03-09 /pmc/articles/PMC5869512/ /pubmed/29522484 http://dx.doi.org/10.3390/v10030119 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dai, Wenwen Wu, Yu Bi, Jinpeng Wang, Shuai Li, Fang Kong, Wei Barbier, Julien Cintrat, Jean-Christophe Gao, Feng Gillet, Daniel Su, Weiheng Jiang, Chunlai Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo |
title | Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo |
title_full | Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo |
title_fullStr | Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo |
title_full_unstemmed | Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo |
title_short | Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo |
title_sort | antiviral effects of abma against herpes simplex virus type 2 in vitro and in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869512/ https://www.ncbi.nlm.nih.gov/pubmed/29522484 http://dx.doi.org/10.3390/v10030119 |
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