ArticleAntiviral research2017
A third component of the human cytomegalovirus terminase complex is involved in letermovir resistance.
Article in Antiviral research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed.
- Article
- Human cytomegalovirus terminase inhibitors letermovir, tomeglovir, and the halogenated benzimidazoles modify DNA cleavage/packaging to generate a super-genomic DNA species by cleavage site skipping.Antiviral research · 2026Article
- The HCMV terminase as an antiviral target: structural insights, inhibitory mechanisms, and the era of letermovir.Frontiers in microbiology · 2026Review
- Emerging Ocular Pathogen Resistance and Clinically Used Solutions: A Problem That Is More than Meets the Eye.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Generation of a panel of mutants that are resistant to standard of care therapies in a clinically relevant strain of human cytomegalovirus for drug resistance profiling.Antiviral research · 2025Article
- Efficacy and safety of rabbit ATLG and ATG in allogeneic hematopoietic stem cell transplantation for children with acquired severe aplastic anemia.Annals of hematology · 2025Article
- Phenotypes of cytomegalovirus genetic variants encountered in a letermovir clinical trial illustrate the importance of genotyping validation.Antiviral research · 2024Article
- Review
- Human Cytomegalovirus (HCMV) Genetic Diversity, Drug Resistance Testing and Prevalence of the Resistance Mutations: A Literature Review.Tropical medicine and infectious disease · 2024Review
- Impact of letermovir prophylaxis in CMV reactivation and disease after allogenic hematopoietic cell transplantation: a real-world, observational study.Annals of hematology · 2024Observational
- Management of Cytomegalovirus Infections in the Era of the Novel Antiviral Players, Letermovir and Maribavir.Infectious disease reports · 2024Review
- Development and validation of a next-generation sequencing assay with open-access analysis software for detecting resistance-associated mutations in CMV.Journal of clinical microbiology · 2023Article
- Inhibiting HCMV pUL89-C Endonuclease with Metal-Binding Compounds.Journal of medicinal chemistry · 2023Review
- Cost Effectiveness of Letermovir for Cytomegalovirus Prophylaxis Compared with Pre-Emptive Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients in the United States.PharmacoEconomics - open · 2023Article
- Cytomegalovirus breakthrough and resistance during letermovir prophylaxis.Bone marrow transplantation · 2023Article
- The Ten Most Common Questions on Cytomegalovirus Infection in Hematopoietic Stem Cell Transplant Patients.Clinical hematology international · 2023Review
- Cytomegalovirus in children undergoing haematopoietic stem cell transplantation: a diagnostic and therapeutic approach to antiviral resistance.Frontiers in pediatrics · 2023Review
- Challenges, Recent Advances and Perspectives in the Treatment of Human Cytomegalovirus Infections.Tropical medicine and infectious disease · 2022Review
- Relative frequency of cytomegalovirus UL56 gene mutations detected in genotypic letermovir resistance testing.Antiviral research · 2022Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
Abstract
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor that was clinically effective in a Phase III prevention trial. In vitro studies have shown that viral mutations conferring letermovir resistance map primarily to the UL56 component of the terminase complex and uncommonly to UL89. After serial culture of a baseline CMV laboratory strain under letermovir, mutation was observed in a third terminase component in 2 experiments, both resulting in amino acid substitution P91S in gene UL51 and adding to a pre-existing UL56 mutation. Recombinant phenotyping indicated that P91S alone conferred 2.1-fold increased letermovir resistance (EC50) over baseline, and when combined with UL56 mutation S229F or R369M, multiplied the level of resistance conferred by those mutations by 3.5-7.7-fold. Similarly a combination of UL56 mutations S229F, L254F and L257I selected in the same experiment conferred 54-fold increased letermovir EC50 over baseline, but 290-fold when combined with UL51 P91S. The P91S mutant was not perceptibly growth impaired. Although pUL51 is essential for normal function of the terminase complex, its biological significance is not well understood. Letermovir resistance mutations mapping to 3 separate genes, and their multiplier effect on the level of resistance, suggest that the terminase components interactively contribute to the structure of a letermovir antiviral target. The diagnostic importance of the UL51 P91S mutation arises from its potential to augment the letermovir resistance of some UL56 mutations at low fitness cost.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.