HCV Mutation Detail Information

Virus Mutation HCV Mutation R155K


Basic Characteristics of Mutations
Mutation Site R155K
Mutation Site Sentence However, the potency is significantly compromised by the drug resistance mutations R155K and D168A.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NS3-4A
Standardized Encoding Gene NS3-4A
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease HCV Infection    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment ASV
Location -
Literature Information
PMID 25243902
Title Structural analysis of asunaprevir resistance in HCV NS3/4A protease
Author Soumana DI,Ali A,Schiffer CA
Journal ACS chemical biology
Journal Info 2014 Nov 21;9(11):2485-90
Abstract Asunaprevir (ASV), an isoquinoline-based competitive inhibitor targeting the hepatitis C virus (HCV) NS3/4A protease, is very potent in vivo. However, the potency is significantly compromised by the drug resistance mutations R155K and D168A. In this study three crystal structures of ASV and an analogue were determined to analyze the structural basis of drug resistance susceptibility. These structures revealed that ASV makes extensive contacts with Arg155 outside the substrate envelope. Arg155 in turn is stabilized by Asp168, and thus when either residue is mutated, the enzyme's interaction with ASV's P2* isoquinoline is disrupted. Adding a P1-P3 macrocycle to ASV enhances the inhibitor's resistance barrier, likely due to poising the inhibitor to its bound conformation. Macrocyclic inhibitors with P2* extension moieties avoiding interaction with the protease S2 residues including Arg155 must be chosen for future design of more robust protease inhibitors.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.