scholarly journals A New Age-Structured Multiscale Model of the Hepatitis C Virus Life-Cycle During Infection and Therapy With Direct-Acting Antiviral Agents

2018 ◽  
Vol 9 ◽  
Author(s):  
Barbara de M. Quintela ◽  
Jessica M. Conway ◽  
James M. Hyman ◽  
Jeremie Guedj ◽  
Rodrigo W. dos Santos ◽  
...  
Keyword(s):  
Life Cycle ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Multiscale Model ◽  
Direct Acting Antiviral ◽  
Virus Life Cycle ◽  
Age Structured ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus

2020 ◽  
Vol 43 (8) ◽  
pp. 418-425
Author(s):  
Maria Isabel Guzman Ramos ◽  
Mercedes Manzano-García ◽  
M. de las Aguas Robustillo-Cortés ◽  
Juan Antonio Pineda ◽  
Ramón Morillo-Verdugo
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Concomitant Medications ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

scholarly journals Computer-aided identification of a series of novel ligands showing high potency as hepatitis C virus NS3/4A protease inhibitors

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Stephen Ejeh ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Stephen E. Abechi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Binding Energy ◽  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Antiviral Agents ◽  
High Potency ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Abstract Background Hepatitis C virus (HCV) is a global medical condition that causes several life-threatening chronic diseases in the liver. The conventional interferon-free treatment regimens are currently in use by a blend of direct-acting antiviral agents (DAAs) aiming at the viral NS3 protease. However, major concerns may be the issue of DAA-resistant HCV strains and the limited availability to the DAAs due to their high price. Due to this crisis, the developments of a new molecule with high potency as an NS3/4A protease inhibitor of the hepatitis-C virus remain a high priority for medical research. This study aimed to use in-silico methods to identify high potent molecule as an NS3/4A protease inhibitor and investigating the binding energy of the identified molecule in comparison with approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) through molecular docking. Results The model obtained by in-silico method have the following statistical records, coefficient of determination (r2) of 0.7704, cross-validation (q2LOO = 0.6914); external test set (r2(pred) = 0.7049) and Y-randomization assessment (cR2p = 0.7025). The results from the model were used to identify 12 new potential human HCV NS3/4A protease inhibitors, and it was observed that the identified molecule is well-fixed when docked with the receptor and was found to have the lowest binding energy of − 10.7, compared to approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) with − 9.5, − 10.0, − 10.5 binding energy, respectively. Conclusion The binding affinity (− 10.7) of the newly identified molecule docked with 3D structures of HCV NS3/4a protease/helicase (PDB ID: 4A92) was found to be better than that of Telaprevir, Simeprevir, and Voxilaprevir (approved direct-acting antiviral agents) which are − 9.5, − 10.0, and − 10.5, respectively. Hence, a novel molecule was identified showing high potency as HCV NS3/4a protease inhibitors.

scholarly journals Current Status of Direct Acting Antiviral Agents against Hepatitis C Virus Infection in Pakistan

Medicina ◽  
2018 ◽  
Vol 54 (5) ◽  
pp. 80 ◽  
Author(s):  
Saba Khaliq ◽  
Syed Raza
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Current Status ◽  
Decompensated Cirrhosis ◽  
Genotype 3 ◽  
Direct Acting Antiviral ◽  
Uridine Nucleotide ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

In Pakistan, the burden of the hepatitis C virus (HCV) infection is the second highest in the world with the development of chronic hepatitis. Interferon-based combination therapy with ribavirin was the only available treatment until a few years back, with severe side-effects and high failure rates against different genotypes of HCV. Interferon-free all-oral direct-acting antiviral agents (DAAs) approved by the FDA have revolutionized the HCV therapeutic landscape due to their efficiency in targeting different genotypes in different categories of patients, including treatment naïve, treatment failure and relapsing patients, as well as patients with compensated and decompensated cirrhosis. The availability and use of these DAAs is limited in the developing world. Sofosbuvir (SOF), a uridine nucleotide analogue and inhibitor of HCV encoded NS5B polymerase, is now a widely available and in-use DAA in Pakistan; whereas daclatasvir was recently added in the list. According to the documented results, there is hope that this disease can be effectively cured in Pakistan, although a few concerns still remain. The aim of this article is to review the effectiveness of DAAs and the current status of this treatment against HCV genotype 3 infection in Pakistan; various factors associated with SVR; its limitations as an effective treatment regime; and future implications.

scholarly journals Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 223 ◽  
Author(s):  
Sara Sobhy Kishta ◽  
Reem El-Shenawy ◽  
Sobhy Ahmed Kishta
Keyword(s):  
Clinical Trials ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Viral Clearance ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs (e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

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