HIV Mutation Detail Information

Virus Mutation HIV Mutation F227L


Basic Characteristics of Mutations
Mutation Site F227L
Mutation Site Sentence Toward double mutant virus strains (F227L + V106A, RES056), (S)-(-)-12a possessed submicromolar antiviral activities.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RT
Standardized Encoding Gene gag-pol:155348
Genotype/Subtype HIV-1
Viral Reference -
Functional Impact and Mechanisms
Disease HIV Infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment NNRTIs
Location -
Literature Information
PMID 32712537
Title Bioisosterism-based design and enantiomeric profiling of chiral hydroxyl-substituted biphenyl-diarylpyrimidine nonnucleoside HIV-1 reverse transcriptase inhibitors
Author Chen X,Ding L,Tao Y,Pannecouque C,De Clercq E,Zhuang C,Chen FE
Journal European journal of medicinal chemistry
Journal Info 2020 Sep 15;202:112549
Abstract The single enantiomers of seven hydroxyl-substituted biphenyl-diarylpyrimidines were designed and synthesized by a bioisosterism strategy as novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). The cellular and enzymatic assays indicated that the novel obtained compounds had significant activities and relatively low cytotoxicity. The supercritical fluid chromatography (SFC) enantioseparations of the racemic compounds and the enantiomeric profiling resulted that the (S) forms were generally more potent than the (R) counterparts. Among all the chiral derivatives, (S)-(-)-12a showed the best potency with the antiviral activities against wild-type (WT) and single mutant strains (L100I, K103 N, Y181C, E138K; especially Y188L), and RT enzyme in the low nanomolar concentration range. Toward double mutant virus strains (F227L + V106A, RES056), (S)-(-)-12a possessed submicromolar antiviral activities. In addition, (S)-(-)-12a showed a high cell-based selectivity index (SI (WT) = 5822) and no apparent toxicity was observed in the in vivo acute toxicity assay and electrocardiogram. The molecular docking studies predicted the binding modes of the compounds with RT and explained the activity differences for the enantiomers. Although the rat pharmacokinetic assay indicated a poor oral metabolism of the hydroxyl compound, the promising antiviral activity of the chiral hydroxyl-substituted biphenyl-diarylpyrimidines provided valuable lead compounds for further anti-HIV drug design.
Sequence Data CCDC1996374;1996375;1996376;1996377;1996378
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.