A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2

Abstract Hepatitis C virus (HCV) entry into hepatocytes is a multistep process that represents a promising target for antiviral intervention. The viral envelope protein E1E2 plays a critical role in HCV entry. In this study, we sought to identify peptide inhibitors of HCV by screening a library of o...

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Autores principales:	Peiqi Yin, Ling Zhang, Fei Ye, Yao Deng, Sha Lu, Yi-Ping Li, Leiliang Zhang, Wenjie Tan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/14a535e894574041ba6a7a01d70ccb93
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spelling	oai:doaj.org-article:14a535e894574041ba6a7a01d70ccb932021-12-02T12:31:50ZA screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E210.1038/s41598-017-04274-82045-2322https://doaj.org/article/14a535e894574041ba6a7a01d70ccb932017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04274-8https://doaj.org/toc/2045-2322Abstract Hepatitis C virus (HCV) entry into hepatocytes is a multistep process that represents a promising target for antiviral intervention. The viral envelope protein E1E2 plays a critical role in HCV entry. In this study, we sought to identify peptide inhibitors of HCV by screening a library of overlapping peptides covering E1E2. Screening the peptide library identified several novel anti-HCV peptides. Four peptides from glycoprotein E2 were selected for further investigation. The 50% effective dose (ED50) was approximately 5 nM for each peptide. Our data indicated that these peptides inhibited HCV entry at the post-attachment step. Moreover, these peptides blocked cell-to-cell transmission of HCVcc and had broad-spectrum antiviral effects on HCVcc. These peptides exhibited combination inhibitory effects on HCVcc infection when combined with IFN-α2b or anti-CD81 antibody. Interestingly, we observed that E2-42 associated with E1 and E2. Our results indicate that E2-42 inhibits HCV entry via E1 and E2. These findings suggest a new avenue for HCV therapeutic development.Peiqi YinLing ZhangFei YeYao DengSha LuYi-Ping LiLeiliang ZhangWenjie TanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Peiqi Yin Ling Zhang Fei Ye Yao Deng Sha Lu Yi-Ping Li Leiliang Zhang Wenjie Tan A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2
description	Abstract Hepatitis C virus (HCV) entry into hepatocytes is a multistep process that represents a promising target for antiviral intervention. The viral envelope protein E1E2 plays a critical role in HCV entry. In this study, we sought to identify peptide inhibitors of HCV by screening a library of overlapping peptides covering E1E2. Screening the peptide library identified several novel anti-HCV peptides. Four peptides from glycoprotein E2 were selected for further investigation. The 50% effective dose (ED50) was approximately 5 nM for each peptide. Our data indicated that these peptides inhibited HCV entry at the post-attachment step. Moreover, these peptides blocked cell-to-cell transmission of HCVcc and had broad-spectrum antiviral effects on HCVcc. These peptides exhibited combination inhibitory effects on HCVcc infection when combined with IFN-α2b or anti-CD81 antibody. Interestingly, we observed that E2-42 associated with E1 and E2. Our results indicate that E2-42 inhibits HCV entry via E1 and E2. These findings suggest a new avenue for HCV therapeutic development.
format	article
author	Peiqi Yin Ling Zhang Fei Ye Yao Deng Sha Lu Yi-Ping Li Leiliang Zhang Wenjie Tan
author_facet	Peiqi Yin Ling Zhang Fei Ye Yao Deng Sha Lu Yi-Ping Li Leiliang Zhang Wenjie Tan
author_sort	Peiqi Yin
title	A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2
title_short	A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2
title_full	A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2
title_fullStr	A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2
title_full_unstemmed	A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2
title_sort	screen for inhibitory peptides of hepatitis c virus identifies a novel entry inhibitor targeting e1 and e2
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/14a535e894574041ba6a7a01d70ccb93
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A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2

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