scholarly journals Molecular Characterization of Hepatitis C Virus for Developed Antiviral Agents Resistance Mutations and New Insights into in-silico Prediction Studies

2020 ◽  
Vol Volume 13 ◽  
pp. 4235-4248
Author(s):  
Mohamed M Adel El-Sokkary ◽  
Lizaveta Gotina ◽  
Mohammad M. Al-Sanea ◽  
Ae Nim Pae ◽  
Rehab Mohammed Elbargisy
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Characterization ◽  
In Silico ◽  
Antiviral Agents ◽  
In Silico Prediction ◽  
Resistance Mutations

scholarly journals VX-950, a Novel Hepatitis C Virus (HCV) NS3-4A Protease Inhibitor, Exhibits Potent Antiviral Activities in HCV Replicon Cells

2006 ◽  
Vol 50 (5) ◽  
pp. 1813-1822 ◽  
Author(s):  
Kai Lin ◽  
Robert B. Perni ◽  
Ann D. Kwong ◽  
Chao Lin
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Alpha Interferon ◽  
Hcv Rna ◽  
Resistance Mutations ◽  
In Vitro Characterization ◽  
Antiviral Activities

ABSTRACT The NS3-4A serine protease of hepatitis C virus (HCV) is essential for viral replication and therefore has been one of the most attractive targets for developing specific antiviral agents against HCV. VX-950, a highly selective, reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, is currently in clinical development for the treatment of hepatitis C. In this report, we describe the in vitro characterization of anti-HCV activities of VX-950 in subgenomic HCV replicon cells. Incubation with VX-950 resulted in a time- and dose-dependent reduction of HCV RNA and proteins in replicon cells. Moreover, following a 2-week incubation with VX-950, a reduction in HCV RNA levels of 4.7 log10 was observed, and this reduction resulted in elimination of HCV RNA from replicon cells, since there was no rebound in replicon RNA after withdrawal of the inhibitor. The combination of VX-950 and alpha interferon was additive to moderately synergistic in reducing HCV RNA in replicon cells with no significant increase in cytotoxicity. The benefit of the combination was sustained over time: a 4-log10 reduction in HCV RNA level was achieved following a 9-day incubation with VX-950 and alpha interferon at lower concentrations than when either VX-950 or alpha interferon was used alone. The combination of VX-950 and alpha interferon also suppressed the emergence of in vitro resistance mutations against VX-950 in replicon cells.

scholarly journals Hepatitis C virus vaccine development: old challenges and new opportunities

2015 ◽  
Vol 2 (3) ◽  
pp. 285-295 ◽  
Author(s):  
Dapeng Li ◽  
Zhong Huang ◽  
Jin Zhong
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Vaccine Development ◽  
Rna Virus ◽  
Antiviral Agents ◽  
Resistance Mutations ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Hepatitis C virus (HCV), an enveloped positive-sense single-stranded RNA virus, can cause chronic and end-stage liver diseases. Approximately 185 million people worldwide are infected with HCV. Tremendous progress has been achieved in the therapeutics of chronic hepatitis C thanks to the development of direct-acting antiviral agents (DAAs), but the worldwide use of these highly effective DAAs is limited due to their high treatment cost. In addition, drug-resistance mutations remain a potential problem as DAAs are becoming a standard therapy for chronic hepatitis C. Unfortunately, no vaccine is available for preventing new HCV infection. Therefore, HCV still imposes a big threat to human public health, and the worldwide eradication of HCV is critically dependent on an effective HCV vaccine. In this review, we summarize recent progresses on HCV vaccine development and present our views on the rationale and strategy to develop an effective HCV vaccine.

scholarly journals Barrier-Independent, Fitness-Associated Differences in Sofosbuvir Efficacy against Hepatitis C Virus

2016 ◽  
Vol 60 (6) ◽  
pp. 3786-3793 ◽  
Author(s):  
Isabel Gallego ◽  
Julie Sheldon ◽  
Elena Moreno ◽  
Josep Gregori ◽  
Josep Quer ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Sensitivity ◽  
Specific Resistance ◽  
Antiviral Agents ◽  
Resistance Mutations ◽  
Coding Region ◽  
High Fitness ◽  
Selection Of

Sofosbuvir displays a high phenotypic barrier to resistance, and it is a component of several combination therapies for hepatitis C virus (HCV) infections. HCV fitness can be a determinant of decreased sensitivity to direct-acting antiviral agents such as telaprevir or daclatasvir, but fitness-dependent decreased drug sensitivity has not been established for drugs with a high phenotypic barrier to resistance. Low- and high-fitness HCV populations and biological clones derived from them were used to infect Huh-7.5 hepatoma cells. Sofosbuvir efficacy was analyzed by measuring virus progeny production during several passages and by selection of possible sofosbuvir resistance mutations determined by sequencing the NS5B-coding region of the resulting populations. Sofosbuvir exhibited reduced efficacy against high-fitness HCV populations, without the acquisition of sofosbuvir-specific resistance mutations. A reduced sofosbuvir efficacy, similar to that observed with the parental populations, was seen for high-fitness individual biological clones. In independently derived high-fitness HCV populations or clones passaged in the presence of sofosbuvir, M289L was selected as the only substitution in the viral polymerase NS5B. In no case was the sofosbuvir-specific resistance substitution S282T observed. High HCV fitness can lead to decreased sensitivity to sofosbuvir, without the acquisition of specific sofosbuvir resistance mutations. Thus, fitness-dependent drug sensitivity can operate with HCV inhibitors that display a high barrier to resistance. This mechanism may underlie treatment failures not associated with selection of sofosbuvir-specific resistance mutations, linked toin vivofitness of pretreatment viral populations.

scholarly journals Molecular characterization of Hepatitis C virus 3a in Peshawar

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gul ◽  
Nabeela Zahid ◽  
Jawad Ahmed ◽  
Fazli Zahir ◽  
Imtiaz Ali Khan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Characterization

Molecular characterization of the human neutralizing response against hepatitis C virus and its role in the prediction of the infection outcome

2013 ◽  
Vol 46 (12) ◽  
pp. 1157
Author(s):  
E. Criscuolo ◽  
F. Cappelletti ◽  
G.A. Sautto ◽  
R.A. Diotti ◽  
N. Clementi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Characterization

Molecular characterization of hepatitis C virus core region in moroccan intravenous drug users

2016 ◽  
Vol 88 (8) ◽  
pp. 1376-1383 ◽  
Author(s):  
Roxana-Delia Trimbitas ◽  
Naouar Fayssel ◽  
Fatima-Zahra Serghini ◽  
Lahcen Wakrim ◽  
Meriem Khyatti ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Characterization ◽  
Drug Users ◽  
Core Region ◽  
Intravenous Drug ◽  
Intravenous Drug Users ◽  
Virus Core
Sign in / Sign up

Export Citation Format

Share Document