Treatment of hepatitis C with protease inhibitors: is resistance a matter of concern?

2013 ◽  
Author(s):  
Philippe Halfon
Keyword(s):  
Hepatitis C ◽  
Protease Inhibitors

Macrocyclic Hepatitis C Virus NS3/4A Protease Inhibitors: An Overview of Medicinal Chemistry

2016 ◽  
Vol 23 (29) ◽  
pp. 3404-3447 ◽  
Author(s):  
Thanigaimalai Pillaiyar ◽  
Vigneshwaran Namasivayam ◽  
Manoj Manickam
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Medicinal Chemistry

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.

Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors

2007 ◽  
Vol 15 (3) ◽  
pp. 1448-1474 ◽  
Author(s):  
Pernilla Örtqvist ◽  
Shane D. Peterson ◽  
Eva Åkerblom ◽  
Thomas Gossas ◽  
Yogesh A. Sabnis ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Ns3 Protease Inhibitors ◽  
Ns3 Protease

scholarly journals Low SVR Rates in Clinical Practice for Treating Genotype 1 Chronic Hepatitis C with Protease Inhibitors Boceprevir and Telaprevir

2014 ◽  
Vol 60 (1) ◽  
pp. 272-274 ◽  
Author(s):  
Perry H. Dubin ◽  
Seth N. Sclair ◽  
Rene Rico ◽  
Amelia K. Boehme ◽  
Emerson Y. Chen ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Clinical Practice ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Chronic Hepatitis C ◽  
Genotype 1

scholarly journals Efficacy and direct costs of chronic hepatitis C treatment with first generation NS3/4A protease inhibitors in a real life population

2016 ◽  
Vol 4 ◽  
pp. 133-137
Author(s):  
Anna Piekarska ◽  
Ewa Koślińska-Berkan ◽  
Kamila Wójcik ◽  
Anna Skubała ◽  
Maciej Jabłkowski ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Chronic Hepatitis C ◽  
First Generation ◽  
Real Life ◽  
Direct Costs ◽  
Hepatitis C Treatment

scholarly journals Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 in Vitro

2021 ◽  
Author(s):  
Karen A. Gammeltoft ◽  
Yuyong Zhou ◽  
Carlos R. Duarte Hernandez ◽  
Andrea Galli ◽  
Anna Offersgaard ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Viral Suppression ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Direct Acting Antiviral ◽  
Human Lung Carcinoma

Antivirals targeting SARS-CoV-2 could improve treatment of COVID-19. We evaluated efficacy of clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PI) against SARS-CoV-2 and their interactions with remdesivir, the only direct-acting antiviral approved for COVID-19 treatment. HCV PI showed differential potency in short-term treatment assays based on detection of SARS-CoV-2 Spike protein in VeroE6 cells. Linear PI boceprevir, telaprevir and narlaprevir had 50% effective concentrations (EC50) of ∼40 μM. Among macrocyclic PI, simeprevir had the highest (EC50 15 μM) and glecaprevir the lowest (EC50 >178 μM) potency, with paritaprevir, grazoprevir, voxilaprevir, vaniprevir, danoprevir and deldeprevir in between. Acyclic PI asunaprevir and faldaprevir had EC50 of 72 and 23 μM, respectively. ACH-806, inhibiting the HCV NS4A protease cofactor, had EC50 of 46 μM. Similar and slightly increased PI potencies were found in human hepatoma Huh7.5 cells and human lung carcinoma A549-hACE2 cells, respectively. Selectivity indexes based on antiviral and cell viability assays were highest for linear PI. In short-term treatments, combination of macrocyclic but not linear PI with remdesivir showed synergism in VeroE6 and A549-hACE2 cells. Longer-term treatment of infected VeroE6 and A549-hACE2 cells with 1-fold EC50 PI revealed minor differences in barrier to SARS-CoV-2 escape. Viral suppression was achieved with 3- to 8-fold EC50 boceprevir or 1-fold EC50 simeprevir or grazoprevir, but not boceprevir, in combination with 0.4- to 0.8-fold EC50 remdesivir; these concentrations did not lead to viral suppression in single treatments. This study could inform development and application of protease inhibitors for optimized antiviral treatments of COVID-19.

scholarly journals Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

Clinics ◽  
2017 ◽  
Vol 72 (6) ◽  
pp. 378-385 ◽  
Author(s):  
LA Callefi ◽  
CA Villela-Nogueira ◽  
SB Tenore ◽  
D Carnaúba-Júnior ◽  
HS Coelho ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Multicenter Study ◽  
Real World ◽  
First Generation ◽  
Genotype 1 ◽  
Virus Genotype
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