HCMV Mutation Detail Information

Virus Mutation HCMV Mutation C325F


Basic Characteristics of Mutations
Mutation Site C325F
Mutation Site Sentence For our analysis, we used three of the most frequent mutations during letermovir treatment, C325F, C325Y and C325W.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region UL56
Standardized Encoding Gene UL56  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment letermovir
Location -
Literature Information
PMID 40133489
Title Identification of a binding pocket of letermovir in the terminase subunit pUL56 of human cytomegalovirus
Author Kmetsch LM,Tietze H,Bogner E
Journal Scientific reports
Journal Info 2025 Mar 25;15(1):10334
Abstract A key step in replication of human cytomegalovirus (HCMV) is the generation and packaging of unit-length genomes into preformed capsids. The enzymes involved in this process are viral terminases. The HCMV terminase consists of two subunits, the ATPase pUL56 and the nuclease pUL89. A potential third component, pUL51, has been proposed. Letermovir is the first terminase inhibitor available for HCMV prophylaxis to allogenic hematopoietic stem cell recipients. However, mutations in the HCMV terminase subunit pUL56 and, to a lesser extent, in pUL89 or pUL51 lead to resistance. Here we focused on the drug target area in the terminase subunit pUL56. To gain further structural insights into the putative binding site of letermovir, in silico analysis of the structure was performed using Phyre2 and SwissDock. For our analysis, we used three of the most frequent mutations during letermovir treatment, C325F, C325Y and C325W. We demonstrated that all variants have a pronounced cavity reduction, leading to the letermovir binding conformations being ""pushed-out"" of the binding pocket. This results in a changed distribution of the Gibbs free binding energy. To circumvent the absolute resistance of C325 mutations a further modification of letermovir might solve the problem and leads to optimizing drug targeting capacity.
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.