scholarly journals The Hepatitis C Virus (HCV) NS4B RNA Binding Inhibitor Clemizole Is Highly Synergistic with HCV Protease Inhibitors

2010 ◽  
Vol 202 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Shirit Einav ◽  
Hadas D. Sobol ◽  
Elizabeth Gehrig ◽  
Jeffrey S. Glenn
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Rna Binding ◽  
Hcv Protease

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 RNA binding protein 24 regulates the translation and replication of hepatitis C virus

2018 ◽  
Vol 9 (11) ◽  
pp. 930-944 ◽  
Author(s):  
Huang Cao ◽  
Kaitao Zhao ◽  
Yongxuan Yao ◽  
Jing Guo ◽  
Xiaoxiao Gao ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals Roles of the AX4GKS and Arginine-Rich Motifs of Hepatitis C Virus RNA Helicase in ATP- and Viral RNA-Binding Activity

2000 ◽  
Vol 74 (20) ◽  
pp. 9732-9737 ◽  
Author(s):  
Shin C. Chang ◽  
Ju-Chien Cheng ◽  
Yi-Hen Kou ◽  
Chuan-Hong Kao ◽  
Chiung-Hui Chiu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Binding ◽  
Atp Hydrolysis ◽  
Nonstructural Protein ◽  
Binding Activity ◽  
Viral Rna ◽  
Atp Binding ◽  
Rna Unwinding ◽  
Arginine Rich Motif

ABSTRACT The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) possesses protease, nucleoside triphosphatase, and helicase activities. Although the enzymatic activities have been extensively studied, the ATP- and RNA-binding domains of the NS3 helicase are not well-characterized. In this study, NS3 proteins with point mutations in the conserved helicase motifs were expressed inEscherichia coli, purified, and analyzed for their effects on ATP binding, RNA binding, ATP hydrolysis, and RNA unwinding. UV cross-linking experiments indicate that the lysine residue in the AX4GKS motif is directly involved in ATP binding, whereas the NS3(GR1490DT) mutant in which the arginine-rich motif (1486-QRRGRTGR-1493) was changed to QRRDTTGR bound ATP as well as the wild type. The binding activity of HCV NS3 helicase to the viral RNA was drastically reduced with the mutation at Arg1488 (R1488A) and was also affected by the K1236E substitution in the AX4GKS motif and the R1490A and GR1490DT mutations in the arginine-rich motif. Previously, Arg1490 was suggested, based on the crystal structure of an NS3-deoxyuridine octamer complex, to directly interact with the γ-phosphate group of ATP. Nevertheless, our functional analysis demonstrated the critical roles of Arg1490 in binding to the viral RNA, ATP hydrolysis, and RNA unwinding, but not in ATP binding.

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