The conformation of hepatitis C virus NS3 proteinase with and without NS4A: a structural basis for the activation of the enzyme by its cofactor

1998 ◽  
Vol 10 (2-3) ◽  
pp. 151-156 ◽  
Author(s):  
Robert A Love ◽  
Hans E Parge ◽  
John A Wickersham ◽  
Zdenek Hostomsky ◽  
Noriyuki Habuka ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Structural Basis

Structural basis for RNA replication by the hepatitis C virus polymerase

Science ◽  
2015 ◽  
Vol 347 (6223) ◽  
pp. 771-775 ◽  
Author(s):  
T. C. Appleby ◽  
J. K. Perry ◽  
E. Murakami ◽  
O. Barauskas ◽  
J. Feng ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Replication ◽  
Structural Basis

scholarly journals Toward a Hepatitis C Virus Vaccine: the Structural Basis of Hepatitis C Virus Neutralization by AP33, a Broadly Neutralizing Antibody

2012 ◽  
Vol 86 (23) ◽  
pp. 12923-12932 ◽  
Author(s):  
J. A. Potter ◽  
A. M. Owsianka ◽  
N. Jeffery ◽  
D. J. Matthews ◽  
Z.-Y. Keck ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Vaccine ◽  
Neutralizing Antibody ◽  
Virus Neutralization ◽  
Structural Basis ◽  
Broadly Neutralizing Antibody

Structural Basis for Resistance of the Genotype 2b Hepatitis C Virus NS5B Polymerase to Site A Non-Nucleoside Inhibitors

2009 ◽  
Vol 390 (5) ◽  
pp. 1048-1059 ◽  
Author(s):  
Edwin H. Rydberg ◽  
Antonella Cellucci ◽  
Linda Bartholomew ◽  
Marco Mattu ◽  
Gaetano Barbato ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Structural Basis ◽  
Nucleoside Inhibitors ◽  
Ns5b Polymerase

scholarly journals Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1

2012 ◽  
Vol 109 (24) ◽  
pp. 9499-9504 ◽  
Author(s):  
L. Kong ◽  
E. Giang ◽  
J. B. Robbins ◽  
R. L. Stanfield ◽  
D. R. Burton ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Neutralizing Antibody ◽  
Virus Neutralization ◽  
Structural Basis ◽  
Broadly Neutralizing Antibody

scholarly journals Unraveling the structural basis of grazoprevir potency against clinically relevant substitutions in hepatitis C virus NS3/4A protease from genotype 1a

2017 ◽  
Vol 292 (15) ◽  
pp. 6202-6212 ◽  
Author(s):  
Zhuyan Guo ◽  
Stuart Black ◽  
Yuan Hu ◽  
Patricia McMonagle ◽  
Paul Ingravallo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Structural Basis ◽  
Genotype 1A

scholarly journals Molecular and Structural Basis for the Roles of Hepatitis C Virus Polymerase NS5B Amino Acids 15, 223, and 321 in Viral Replication and Drug Resistance

2014 ◽  
Vol 58 (11) ◽  
pp. 6861-6869 ◽  
Author(s):  
Angela M. Lam ◽  
Thomas E. Edwards ◽  
Ralph T. Mosley ◽  
Eisuke Murakami ◽  
Shalini Bansal ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Replication ◽  
Rna Binding ◽  
Nonstructural Protein ◽  
Point Mutations ◽  
Resistance Mutation ◽  
Structural Basis ◽  
Nucleoside Triphosphate ◽  
Multiple Point

ABSTRACTResistance to the 2′-F-2′-C-methylguanosine monophosphate nucleotide hepatitis C virus (HCV) inhibitors PSI-352938 and PSI-353661 was associated with a combination of amino acid changes (changes of S to G at position 15 [S15G], C223H, and V321I) within the genotype 2a nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase. To understand the role of these residues in viral replication, we examined the effects of single and multiple point mutations on replication fitness and inhibition by a series of nucleotide analog inhibitors. An acidic residue at position 15 reduced replicon fitness, consistent with its proximity to the RNA template. A change of the residue at position 223 to an acidic or large residue reduced replicon fitness, consistent with its proposed proximity to the incoming nucleoside triphosphate (NTP). A change of the residue at position 321 to a charged residue was not tolerated, consistent with its position within a hydrophobic cavity. This triple resistance mutation was specific to both genotype 2a virus and 2′-F-2′-C-methylguanosine inhibitors. A crystal structure of the NS5B S15G/C223H/V321I mutant of the JFH-1 isolate exhibited rearrangement to a conformation potentially consistent with short primer-template RNA binding, which could suggest a mechanism of resistance accomplished through a change in the NS5B conformation, which was better tolerated by genotype 2a virus than by viruses of other genotypes.

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