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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 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-?2b 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.

SUBMITTER: Yin P 

PROVIDER: S-EPMC5479846 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Yin Peiqi P   Zhang Ling L   Ye Fei F   Deng Yao Y   Lu Sha S   Li Yi-Ping YP   Zhang Leiliang L   Tan Wenjie W  

Scientific reports 20170621 1


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 (  ...[more]

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