HIV Mutation Detail Information

Virus Mutation HIV Mutation K101P


Basic Characteristics of Mutations
Mutation Site K101P
Mutation Site Sentence The DeltaS + DeltaA values for K101P suggest that this mutation confers intermediate/high-level resistance to MIV-150, but remains susceptible to doravirine.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RT
Standardized Encoding Gene gag-pol:155348
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease HIV Infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment NNRTIs;doravirine
Location -
Literature Information
PMID 32493197
Title Application of Structure-based Methods to Analyze Resistance Mutations for Chemically Diverse Non-Nucleoside Reverse Transcriptase Inhibitors
Author Tabassum T,Azeem SM,Muwonge AN,Frey KM
Journal Current HIV research
Journal Info 2020;18(4):283-291
Abstract BACKGROUND: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are used in combination with antiretroviral therapy to suppress viral loads in HIV patients. The chemical design of NNRTIs has changed in recent years in response to resistance-associated mutations (RAMs) and resistance. NNRTIs are chemically diverse compounds that bind an allosteric site of HIV RT. Resistance- associated mutations (RAMs) identified in HIV patients are associated with NNRTI resistance. RAMs confer amino acid changes that alter both structural and physiochemical properties of the allosteric site. Ultimately, these changes reduce NNRTI affinity. Previously, we used a combination of computational and experimental methods to analyze and validate RAMs for 3 diarylpyrimidine (DAPY) NNRTIs. OBJECTIVE: The objective of this study is to apply these methods to other chemically diverse, non- DAPY NNRTIs. MATERIALS AND METHODS: We selected MIV-150 (experimental microbicide) and doravirine for this study. A computational and molecular modeling strategy was used to evaluate the effects of RAMs. Calculated changes in drug affinity and stability (DeltaS + DeltaA) were used to determine overall resistance levels: susceptible, low, intermediate, and high. The DeltaS + DeltaA values for K101P suggest that this mutation confers intermediate/high-level resistance to MIV-150, but remains susceptible to doravirine. Based on the determined resistance levels, we analyzed the models and used Molecular Dynamics (MD) to compare the interactions of MIV-150/doravirine with RT wild-type (WT) and RT (K101P). From MD, we found that key interactions were lost with RT (K101P), but were retained with doravirine. To experimentally validate our findings, we conducted a fluorescence-based reverse transcription assay for MIV-150 with RT (WT) and RT (K101P). IC50 values determined in assays showed a 101-fold change in potency for MIV-150, but essentially no change for doravirine. RESULTS: Our computational and experimental results are also consistent with antiviral data reported in the literature. CONCLUSION: We believe that this approach is effective for analyzing mutations to determine resistance profiles for chemically diverse NNRTIs in development.
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.