IV Mutation Detail Information

Virus Mutation IV Mutation G147R


Basic Characteristics of Mutations
Mutation Site G147R
Mutation Site Sentence Molecular dynamics study on the effect of the N1 neuraminidase double mutant G147R/H274Y on oseltamivir sensitivity .
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NA
Standardized Encoding Gene NA
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Influenza A     Influenza B    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment oseltamivir
Location -
Literature Information
PMID 39659606
Title Molecular dynamics study on the effect of the N1 neuraminidase double mutant G147R/H274Y on oseltamivir sensitivity
Author Nurrohman AI,Suwito H,Puspaningsih NNT,Haq KU
Journal RSC advances
Journal Info 2024 Dec 10;14(52):39017-39026
Abstract Inhibition of neuraminidase is the most prominent target in influenza medication using oseltamivir as an inhibitor. However, the emerging resistance of neuraminidase toward oseltamivir due to mutation reduces the efficacy of oseltamivir. The generally reported mutation is a single mutation at H274Y, which declines the sensitivity of oseltamivir by almost 900 folds compared to the wild-type variant. Moreover, an additional mutation at G147R increases the resistance by more than 2000 folds. However, sufficient studies on the resistance mechanism of this variant have not yet been reported. Therefore, we simulated four neuraminidase proteins comprising wild-type (WT), G147R, H274Y, and G147R/H274Y using molecular dynamics simulation to disclose the binding mechanism of oseltamivir. Trajectory analysis was conducted to reveal structural stability and flexibility. Furthermore, end-point free binding energy calculations were conducted. The energy decomposition of each residue was also calculated. The end-point energy calculation showed a similar result to that of experimental data. The energy decomposition analysis revealed that G147R/H274Y showed significant reduction in oseltamivir (OST) interaction with R118. Salt-bridge disruption caused by R224-E276 was also observed. Modification to enhance the polarity of the inhibitor might be useful in overcoming these changes. However, it should be noted that such changes could worsen the pharmacokinetic property of the inhibitor. It is hoped that these findings will provide useful insights for the development of an anti-influenza drug that can withstand the mutant variant.
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.