Differential Efficacy of Protease Inhibitors Against HCV Genotypes 2a, 3a, 5a, and 6a NS3/4A Protease Recombinant Viruses

Gottwein, Judith M.; Scheel, Troels K. H.; Jensen, Tanja B.; Ghanem, Lubna; Bukh, Jens

doi:10.1053/j.gastro.2011.06.004

Cited by 134 publications

(184 citation statements)

References 25 publications

Supporting

Mentioning

171

Contrasting

Order By: Relevance

“…1). Supporting this observation, we and others previously showed that IFN-␣ treatment suppressed viral infection in Huh7.5 cells (24,38,40,(45)(46)(47). In addition, in cells from a typical transfection experiment, as shown in Fig.…”

Section: Discussionsupporting

confidence: 75%

“…To investigate significance of the observed differences in percent residual infectivity as shown in Fig. 4C, we carried out statistical analysis as previously described (38). Median 50% effective concentrations (EC 50 ) with 95% confidence intervals (CI) were 0.22 (0.16 to 0.29), 5.0 (3.6 to 7.0), and 15.5 (13.8 to 17.5) IU/ml for 1a(H77), 1a(H77)I348T, and 1a(H77)5mut, respectively.…”

Section: Fig 5 I348t In E1 Increased Infectivity Titers Of 1a(h77) Anmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Alpha Interferon-Induced Envelope Mutations of Hepatitis C Virus In Vitro Associated with Increased Viral Fitness and Interferon Resistance

Serre

Krarup

Bukh

et al. 2013

J Virol

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 75%

Section: Fig 5 I348t In E1 Increased Infectivity Titers Of 1a(h77) Anmentioning

confidence: 99%

Identification of Alpha Interferon-Induced Envelope Mutations of Hepatitis C Virus In Vitro Associated with Increased Viral Fitness and Interferon Resistance

Serre

Krarup

Bukh

et al. 2013

J Virol

Self Cite

View full text Add to dashboard Cite

“…Future regimens will incorporate multiple new agents directly targeting the virus to increase the efficacy of treatment. The protease inhibitors have entered into the clinic for HCV-infected individuals recently (24). There will be plenty of patients resistant to the current therapy (25,26).…”

Section: Figmentioning

confidence: 99%

Inhibition of Hepatitis C Virus Production by Aptamers against the Core Protein

Shi

Gao

et al. 2014

J Virol

View full text Add to dashboard Cite

bHepatitis C virus (HCV) core protein is essential for virus assembly. HCV core protein was expressed and purified. Aptamers against core protein were raised through the selective evolution of ligands by the exponential enrichment approach. Detection of HCV infection by core aptamers and the antiviral activities of aptamers were characterized. The mechanism of their anti-HCV activity was determined. The data showed that selected aptamers against core specifically recognize the recombinant core protein but also can detect serum samples from hepatitis C patients. Aptamers have no effect on HCV RNA replication in the infectious cell culture system. However, the aptamers inhibit the production of infectious virus particles. Beta interferon (IFN-␤) and interferon-stimulated genes (ISGs) are not induced in virally infected hepatocytes by aptamers. Domains I and II of core protein are involved in the inhibition of infectious virus production by the aptamers. V31A within core is the major resistance mutation identified. Further study shows that the aptamers disrupt the localization of core with lipid droplets and NS5A and perturb the association of core protein with viral RNA. The data suggest that aptamers against HCV core protein inhibit infectious virus production by disrupting the localization of core with lipid droplets and NS5A and preventing the association of core protein with viral RNA. The aptamers for core protein may be used to understand the mechanisms of virus assembly. Core-specific aptamers may hold promise for development as early diagnostic reagents and potential therapeutic agents for chronic hepatitis C.

show abstract

“…For instance, variations in NS3-V170 are present in most HCV genotype 1 isolates, and polymorphism in NS3-D168 is characteristic of HCV genotype 3 [32] . As the development of NS3/4A PIs was based in HCV genotype 1, subtype 1b, their antiviral activity with non-1b genotypes, may be not as effective, although some PIs inhibit more than one HCV genotype [22,42,[48][49][50] . Currently neither Boceprevir nor Telaprevir should be used in patients infected with HCV genotypes other than 1.…”

Section: Hcv Resistance To Ns3/4a Pismentioning

confidence: 99%

Hepatitis C virus resistance to new specifically-targeted antiviral therapy: A public health perspective

Salvatierra

Fareleski²,

Forcada³

et al. 2013

WJV

View full text Add to dashboard Cite

Until very recently, treatment for chronic hepatitis C virus (HCV) infection has been based on the combination of two non-viral specific drugs: pegylated interferon-α and ribavirin, which is effective in, overall, about 40%-50% of cases. To improve the response to treatment, novel drugs have been designed to specifically block viral proteins. Multiple compounds are under development, and the approval for clinical use of the first of such direct-acting antivirals in 2011 (Telaprevir and Boceprevir), represents a milestone in HCV treatment. HCV therapeutics is entering a new expanding era, and a highly-effective cure is envisioned for the first time since the discovery of the virus in 1989. However, any antiviral treatment may be limited by the capacity of the virus to overcome the selective pressure of new drugs, generating antiviral resistance. Here, we try to provide a basic overview of new treatments, HCV resistance to new antivirals and some considerations derived from a Public Health perspective, using HCV resistance to protease and polymerase inhibitors as examples.

show abstract

Differential Efficacy of Protease Inhibitors Against HCV Genotypes 2a, 3a, 5a, and 6a NS3/4A Protease Recombinant Viruses

Cited by 134 publications

References 25 publications

Identification of Alpha Interferon-Induced Envelope Mutations of Hepatitis C Virus In Vitro Associated with Increased Viral Fitness and Interferon Resistance

Identification of Alpha Interferon-Induced Envelope Mutations of Hepatitis C Virus In Vitro Associated with Increased Viral Fitness and Interferon Resistance

Inhibition of Hepatitis C Virus Production by Aptamers against the Core Protein

Hepatitis C virus resistance to new specifically-targeted antiviral therapy: A public health perspective

Contact Info

Product

Resources

About