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Journal article
Inhibitors of Endoplasmic Reticulum alpha-Glucosidases Potently Suppress Hepatitis C Virus Virion Assembly and Release
Antimicrobial agents and chemotherapy, v 55(3), pp 1036-1044
01 Mar 2011
PMID: 21173177
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
alpha-Glucosidases I and II are endoplasmic reticulum-resident enzymes that are essential for N-linked glycan processing and subsequent proper folding of glycoproteins. In this report, we first demonstrate that down-regulation of the expression of alpha-glucosidase I, II, or both in Huh7.5 cells by small hairpin RNA technology inhibited the production of hepatitis C virus (HCV). In agreement with the essential role of alpha-glucosidases in HCV envelope glycoprotein processing and folding, treatment of HCV-infected cells with a panel of imino sugar derivatives, which are competitive inhibitors of alpha-glucosidases, did not affect intracellular HCV RNA replication and nonstructural protein expression but resulted in the inhibition of glycan processing and subsequent degradation of HCV E2 glycoprotein. As a consequence, HCV virion assembly and secretion were inhibited. In searching for imino sugars with better antiviral activity, we found that a novel imino sugar, PBDNJ0804, had a superior ability to inhibit HCV virion assembly and secretion. In summary, we demonstrated that glucosidases are important host factor-based antiviral targets for HCV infection. The low likelihood of drug-resistant virus emergence and potent antiviral efficacy of the novel glucosidase inhibitor hold promise for its development as a therapeutic agent for the treatment of chronic hepatitis C.
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Details
- Title
- Inhibitors of Endoplasmic Reticulum alpha-Glucosidases Potently Suppress Hepatitis C Virus Virion Assembly and Release
- Creators
- Xiaowang Qu - Drexel UniversityXiaoben Pan - Drexel Univ, Coll Med, Drexel Inst Biotechnol & Virol Res, Dept Microbiol & Immunol, Doylestown, PA 18902 USAJessica Weidner - Drexel UniversityWenquan Yu - Hepatitis B FoundationDominic Alonzi - University of OxfordXiaodong Xu - Hepatitis B FoundationTerry Butters - University of OxfordTimothy Block - Drexel UniversityJu-Tao Guo - Drexel UniversityJinhong Chang - Drexel University
- Publication Details
- Antimicrobial agents and chemotherapy, v 55(3), pp 1036-1044
- Publisher
- Amer Soc Microbiology
- Number of pages
- 9
- Grant note
- Hepatitis B Foundation through Commonwealth of Pennsylvania U01AI061441 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) AI061441 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000287687100012
- Scopus ID
- 2-s2.0-79952322370
- Other Identifier
- 991019167653804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy