ArticleJournal of virology2011
The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04904614 (Evaluation of the Tolerability and Clinical Effectiveness of Letermovir in Heart Transplantation), which is not on this map. Cited by 143 papers.
What it found
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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.
Evaluation of the Tolerability and Clinical Effectiveness of Letermovir in Heart Transplantation
Who cites it
143 citing papers in PubMed, 333 citations in OpenAlex.
- Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients.CPT: pharmacometrics & systems pharmacology · 2021Trial
- A Mortality Analysis of Letermovir Prophylaxis for Cytomegalovirus (CMV) in CMV-seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Trial
- Intravenous Hydroxypropyl β-Cyclodextrin Formulation of Letermovir: A Phase I, Randomized, Single-Ascending, and Multiple-Dose Trial.Clinical and translational science · 2017Trial
- Something old, something new? Herpesvirus genome packaging examined in light of lessons from the tailed bacteriophages.Journal of virology · 2026Review
- Dissecting the dsDNA viral packaging machinery: structural evolution and potential for therapeutics.Journal of virology · 2026Review
- A real-world study on different initiation times and treatment durations of letermovir for cytomegalovirus prophylaxis after allogeneic haematopoietic stem cell transplantation.British journal of haematology · 2026Article
- Human Cytomegalovirus Genetic Diversity, Clinical Relevance, and Emerging Insights.Reviews in medical virology · 2026Review
- A novel inhibitor of human cytomegalovirus acts through a specific antiviral mechanism that involves the helicase-primase complex.Antimicrobial agents and chemotherapy · 2026Article
- 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
- Computational Investigation of Novel pUL56 Ligands Using Docking and Molecular Dynamics with Preliminary Cytotoxicity Evaluation: An Early-Stage Study.Molecules (Basel, Switzerland) · 2026Article
- The HCMV terminase as an antiviral target: structural insights, inhibitory mechanisms, and the era of letermovir.Frontiers in microbiology · 2026Review
- Letermovir does not affect long-term polyclonal immune reconstitution after allogeneic hematopoietic stem cell transplantation with ATG-based GvHD prophylaxis.Frontiers in immunology · 2026Article
- Discovery of a Baloxavir-Inspired Endonuclease Inhibitor That Prevents Herpes Simplex Virus 1 Replication in Cell Culture and In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tandem Synthesis of Tetrahydropyrroloquinazolines and Related Polyannular Scaffolds.The Journal of organic chemistry · 2025Article
- Interaction of human cytomegalovirus pUL52 with major components of the viral DNA encapsidation network underlines its essential role in genome cleavage-packaging.Journal of virology · 2025Article
- Identification of a binding pocket of letermovir in the terminase subunit pUL56 of human cytomegalovirus.Scientific reports · 2025Article
- Letermovir Treatment for Refractory or Resistant Cytomegalovirus Infection or Disease or with Concurrent Organ Dysfunction: A Phase 2 Open Label Study.Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada · 2025Article
- Letermovir prophylaxis for cytomegalovirus in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.Bone marrow transplantation · 2025Article
- Revealing the Unseen: Next-Generation Sequencing for Early Detection of Drug-Resistant Cytomegalovirus Variants Upon Letermovir Prophylaxis Failure.The Journal of infectious diseases · 2025Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cytomegalovirus (HCMV) remains the leading viral cause of birth defects and life-threatening disease in transplant recipients. All approved antiviral drugs target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Attempts to discover improved anti-HCMV drugs led to the identification of the small-molecular-weight compound AIC246 (Letermovir). AIC246 exhibits outstanding anti-HCMV activity in vitro and in vivo and currently is undergoing a clinical phase IIb trial. The initial mode-of-action studies suggested that the drug acts late in the HCMV replication cycle via a mechanism distinct from that of polymerase inhibitors. Here, we extend our mode-of-action analyses and report that AIC246 blocks viral replication without inhibiting the synthesis of progeny HCMV DNA or viral proteins. The genotyping of mutant viruses that escaped AIC246 inhibition uncovered distinct point mutations in the UL56 subunit of the viral terminase complex. Marker transfer analyses confirmed that these mutations were sufficient to mediate AIC246 resistance. The mapping of drug resistance to open reading frame UL56 suggests that viral DNA processing and/or packaging is targeted by AIC246. In line with this, we demonstrate that AIC246 affects the formation of proper unit-length genomes from viral DNA concatemers and interferes with virion maturation. However, since AIC246-resistant viruses do not exhibit cross-resistance to previously published terminase inhibitors, our data suggest that AIC246 interferes with HCMV DNA cleavage/packaging via a molecular mechanism that is distinct from that of other compound classes known to target the viral terminase.
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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.