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Gem

Clinically Approved Ion Channel Inhibitors Close Gates for Hepatitis C Virus and Open Doors for Drug Repurposing in Infectious Viral Diseases

Thomas Pietschmann
Michaela Ulrike Gack, Editor
Thomas Pietschmann
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Michaela Ulrike Gack
Harvard Medical School
Roles: Editor
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DOI: 10.1128/JVI.01914-16
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    FIG 1

    Schematic representations of the HCV genome organization, the virus and replication complex structures, and the replication cycle. (A) The HCV genome encodes highly structured 5′ and 3′ nontranslated regions (NTRs) needed for polyprotein translation and RNA replication. Key functions of individual proteins are highlighted, and the three major drug targets addressed by licensed directly acting antivirals are indicated. The suffixes identifying the different drug classes are printed in capital letters. The HCV particle consists of viral factors and human lipoproteins, and RNA replication complexes are composed of viral NS3 to NS5B proteins and host factors enclosed in endoplasmic reticulum (ER)-derived double-membrane vesicles. RNA Pol., RNA polymerase. (B) HCV attaches to hepatocytes by binding to glycosaminoglycans and SR-B1, and it translocates to tight junctions, where it is endocytosed through clathrin-mediated endocytosis. The viral genome is delivered into the cytoplasm through a low-pH-triggered fusion process that involves the E1 and E2 glycoproteins.

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    FIG 2

    Overview of related chemical compounds that were recently identified as HCV entry inhibitors. Basic chemical scaffolds used to categorize the compounds highlighted here and mentioned in the text are depicted at the top left. The typical clinical uses and targets of these compounds (according to the respective PubChem entries) are given, and the publications that reported the anti-HCV activities of the given molecules are indicated. Ref., reference; Applicat., application; chan., channel; r., receptor.

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Clinically Approved Ion Channel Inhibitors Close Gates for Hepatitis C Virus and Open Doors for Drug Repurposing in Infectious Viral Diseases
Thomas Pietschmann
Journal of Virology Jan 2017, 91 (2) e01914-16; DOI: 10.1128/JVI.01914-16

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Clinically Approved Ion Channel Inhibitors Close Gates for Hepatitis C Virus and Open Doors for Drug Repurposing in Infectious Viral Diseases
Thomas Pietschmann
Journal of Virology Jan 2017, 91 (2) e01914-16; DOI: 10.1128/JVI.01914-16
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    • ABSTRACT
    • HCV AND HEPATITIS C: FROM THE UNKNOWN CULPRIT TO THE FIRST CURABLE CHRONIC VIRAL INFECTION
    • ION CHANNEL INHIBITORS AND RELATED ANTIHISTAMINES AS FIRST-IN-CLASS HCV MEMBRANE FUSION INHIBITORS
    • ACKNOWLEDGMENTS
    • REFERENCES
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KEYWORDS

antiviral agents
Drug Repositioning
hepacivirus
Hepatitis C
Ion Channel Gating
Ion Channels
cell entry
drug repurposing
fusion inhibitor
hepatitis C virus
infectious disease
ion channel inhibitors
membrane fusion

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