HIV Mutation Detail Information

Virus Mutation HIV Mutation D30N


Basic Characteristics of Mutations
Mutation Site D30N
Mutation Site Sentence Insights into the interaction mechanism of first-generation HIV-1 protease inhibitors with wild-type and mutant (D30N and L76V) enzymes through in-silico based approach.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region PR
Standardized Encoding Gene gag-pol  
Genotype/Subtype HIV-1
Viral Reference -
Functional Impact and Mechanisms
Disease HIV Infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment "PR inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir"
Location -
Literature Information
PMID 39960065
Title Insights into the interaction mechanism of first-generation HIV-1 protease inhibitors with wild-type and mutant (D30N and L76V) enzymes through in-silico based approach
Author S P,S J
Journal Journal of biomolecular structure & dynamics
Journal Info 2025 Feb 17:1-13
Abstract The combined effort of medical, scientific and pharmaceutical research has transformed the HIV infection from an inevitably fatal disease into a manageable chronic ailment. Especially after the introduction of protease (PR) inhibitors the efficacy of the treatment regimen has been increased. However, the development of mutant PR enzymes is a major concern. The present study focuses on to understand the alterations in wild-type and mutants (D30N and L76V) PR structure by interaction of first-generation PR inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir. This information is extracted using molecular docking and MD simulation. Further, post-MD analysis such as RMSD, RMSF, PCA, DCCM, intermolecular interactions and binding free energy values calculation has been done. In comparison to L76V, D30N mutation affected the stable binding of the most of the studied PR inhibitors. The positively charged NH2 and thiazole group of amprenavir and nelfinavir is repelled by NH2 of Asn30 in D30N mutant. This repulsion pushes the drugs towards flap domain and causes flap opening. The MD simulation reveals that amprenavir, nelfinavir and saquinavir drugs have good compatibility with L76V mutant PR enzyme whereas indinavir was affected by the same. L76V mutant does not form any direct interaction with the first line drugs; hence the drugs forming strong interactions with the active site, flap domain and substrate binding region residues are quite enough to manage the resistance provided by L76V mutant. The results provided the insight into the drug-resistant or drug-susceptibility mechanism of L76V and D30N mutation against first-generation PR 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.