ArticleNature communications2021
NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Nelarabine in T-cell acute lymphoblastic leukemia: intracellular metabolism and molecular mode-of-action.Leukemia · 2025Pooled it
- Development of ganciclovir as an anti-human cytomegalovirus drug: historical perspectives and future prospects.The Journal of general virology · 2026Review
- Effect of interferon combined with ganciclovir on immune status in children with infectious mononucleosis.Pakistan journal of medical sciences · 2025Article
- Optimization of Preemptive Therapy for Cytomegalovirus Infections With Valganciclovir Based on Therapeutic Drug Monitoring: Protocol for a Phase II, Single-Center, Single-Arm Trial.JMIR research protocols · 2025Article
- Pilot Study of Valganciclovir-Induced Leukopenia in Kidney Transplant Recipients WithKidney international reports · 2024Article
- Development and Validation of an HPLC-UV Method for the Quantification of Acyclovir and Ganciclovir in the Plasma of Pediatric Immunocompromised Patients.International journal of molecular sciences · 2024Article
- Chromosome 8p engineering reveals increased metastatic potential targetable by patient-specific synthetic lethality in liver cancer.Science advances · 2023Article
- Long-read HiFi sequencing of NUDT15: Phased full-gene haplotyping and pharmacogenomic allele discovery.Human mutation · 2022Article
- Low NUDT15 expression levels due to biallelic NUDT15 variants and 6-mercaptopurine intolerance.British journal of haematology · 2022Article
- Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients.Frontiers in pharmacology · 2022Article
- NUDT15 Genetic Polymorphism as a Risk Factor for Early Neutropenia During Valganciclovir Prophylaxis in Lung Transplant Patients.Transplant infectious disease : an official journal of the Transplantation SocietyArticle
- Associations of Nucleoside Diphosphate-Linked Moiety X-Type Motif 15 Variants With Neutropenia During Antiviral Therapy for Cytomegalovirus Disease in Pediatric Liver Transplant Recipients.Transplant infectious disease : an official journal of the Transplantation SocietyArticle
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabolized by NUDT15. NUDT15 hydrolyzes ACV and GCV triphosphate metabolites, reducing their effects against cytomegalovirus (CMV) in vitro. Loss of NUDT15 potentiates cytotoxicity of ACV and GCV in host cells. In hematopoietic stem cell transplant patients, the risk of CMV viremia following ACV prophylaxis is associated with NUDT15 genotype (P = 0.015). Donor NUDT15 deficiency is linked to graft failure in patients receiving CMV-seropositive stem cells (P = 0.047). In conclusion, NUDT15 is an important metabolizing enzyme for ACV and GCV, and NUDT15 variation contributes to inter-patient variability in their therapeutic effects.
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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 Socratic graph.