Modeling the antiviral activity of ribavirin against hepatitis C virus in cell culture

Hepatology ◽  
2013 ◽  
Vol 58 (4) ◽  
pp. 1203-1206
Author(s):  
Daniel J. Felmlee ◽  
Fei Xiao ◽  
Thomas F. Baumert
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity

scholarly journals Selective Inhibition of Hepatitis C Virus Infection by Hydroxyzine and Benztropine

2014 ◽  
Vol 58 (6) ◽  
pp. 3451-3460 ◽  
Author(s):  
Lidia Mingorance ◽  
Martina Friesland ◽  
Mairene Coto-Llerena ◽  
Sofía Pérez-del-Pulgar ◽  
Loreto Boix ◽  
...  
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Viral Entry ◽  
Selective Inhibition ◽  
Chemical Library ◽  
Effective Components ◽  
Severe Liver Disease ◽  
Cell Culture Assay

ABSTRACTHepatitis C virus (HCV) infection is a major biomedical problem worldwide as it causes severe liver disease in millions of humans around the world. Despite the recent approval of specific drugs targeting HCV replication to be used in combination with alpha interferon (IFN-α) and ribavirin, there is still an urgent need for pangenotypic, interferon-free therapies to fight this genetically diverse group of viruses. In this study, we used an unbiased screening cell culture assay to interrogate a chemical library of compounds approved for clinical use in humans. This system enables identifying nontoxic antiviral compounds targeting every aspect of the viral life cycle, be the target viral or cellular. The aim of this study was to identify drugs approved for other therapeutic applications in humans that could be effective components of combination therapies against HCV. As a result of this analysis, we identified 12 compounds with antiviral activity in cell culture, some of which had previously been identified as HCV inhibitors with antiviral activity in cell culture and had been shown to be effective in patients. We selected two novel HCV antivirals, hydroxyzine and benztropine, to characterize them by determining their specificity and genotype spectrum as well as by defining the step of the replication cycle targeted by these compounds. We found that both compounds effectively inhibited viral entry at a postbinding step of genotypes 1, 2, 3, and 4 without affecting entry of other viruses.

scholarly journals Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system

Hepatology ◽  
2006 ◽  
Vol 44 (6) ◽  
pp. 1626-1634 ◽  
Author(s):  
Muriel Lavie ◽  
Cécile Voisset ◽  
Ngoc Vu-Dac ◽  
Virginie Zurawski ◽  
Gilles Duverlie ◽  
...  
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Culture System ◽  
Serum Amyloid A ◽  
Virus Entry ◽  
Cell Culture System ◽  
Amyloid A ◽  
A Cell

scholarly journals Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

2012 ◽  
Vol 9 (1) ◽  
pp. 143 ◽  
Author(s):  
Feyza Gunduz ◽  
Fatma M Aboulnasr ◽  
Partha K Chandra ◽  
Sidhartha Hazari ◽  
Bret Poat ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Er Stress ◽  
Free Fatty Acids ◽  
Interferon Alpha

Investigations into the receptor requirements of Hepatitis C Virus (HCV) pseudoparticles and cell culture grown virions

2006 ◽  
Vol 44 (01) ◽  
Author(s):  
T von Hahn ◽  
M Flint ◽  
BD Lindenbach ◽  
A Boullier ◽  
O Quehenberger ◽  
...  
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C

scholarly journals Ultrastructural and Biophysical Characterization of Hepatitis C Virus Particles Produced in Cell Culture

2010 ◽  
Vol 84 (21) ◽  
pp. 10999-11009 ◽  
Author(s):  
Pablo Gastaminza ◽  
Kelly A. Dryden ◽  
Bryan Boyd ◽  
Malcolm R. Wood ◽  
Mansun Law ◽  
...  
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Structural Characteristics ◽  
Buoyant Density ◽  
Hcv Rna ◽  
Membrane Bilayer ◽  
Biophysical Characterization ◽  
Negative Stain ◽  
A Minor

ABSTRACT We analyzed the biochemical and ultrastructural properties of hepatitis C virus (HCV) particles produced in cell culture. Negative-stain electron microscopy revealed that the particles were spherical (∼40- to 75-nm diameter) and pleomorphic and that some of them contain HCV E2 protein and apolipoprotein E on their surfaces. Electron cryomicroscopy revealed two major particle populations of ∼60 and ∼45 nm in diameter. The ∼60-nm particles were characterized by a membrane bilayer (presumably an envelope) that is spatially separated from an internal structure (presumably a capsid), and they were enriched in fractions that displayed a high infectivity-to-HCV RNA ratio. The ∼45-nm particles lacked a membrane bilayer and displayed a higher buoyant density and a lower infectivity-to-HCV RNA ratio. We also observed a minor population of very-low-density, >100-nm-diameter vesicular particles that resemble exosomes. This study provides low-resolution ultrastructural information of particle populations displaying differential biophysical properties and specific infectivity. Correlative analysis of the abundance of the different particle populations with infectivity, HCV RNA, and viral antigens suggests that infectious particles are likely to be present in the large ∼60-nm HCV particle populations displaying a visible bilayer. Our study constitutes an initial approach toward understanding the structural characteristics of infectious HCV particles.

Neutralizing Antibodies Induced by Cell Culture–Derived Hepatitis C Virus Protect Against Infection in Mice

2013 ◽  
Vol 145 (2) ◽  
pp. 447-455.e4 ◽  
Author(s):  
Daisuke Akazawa ◽  
Masaki Moriyama ◽  
Hiroshi Yokokawa ◽  
Noriaki Omi ◽  
Noriyuki Watanabe ◽  
...  
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Neutralizing Antibodies
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