ArticleAntiviral research2013
Ribonucleotide reductase inhibitors hydroxyurea, didox, and trimidox inhibit human cytomegalovirus replication in vitro and synergize with ganciclovir.
Article in Antiviral research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- 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
- Downregulation of the host ribonucleotide reductase subunit M2 via the Wnt/β-catenin pathway is a novel mechanism for duck plague virus replication and a potential antiviral target.Poultry science · 2026Article
- Macrophage-mediated delivery of ganciclovir nanocomplexes inhibits the pathogenicity of Kaposi's sarcoma-associated herpesvirus.Discover oncology · 2025Article
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- Proteome-Based Investigation Identified Potential Drug Repurposable Small Molecules Against Monkeypox Disease.Molecular biotechnology · 2024Article
- Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers.Pharmaceutics · 2023Article
- Hepatitis C Virus Down-Regulates the Expression of Ribonucleotide Reductases to Promote Its Replication.Pathogens (Basel, Switzerland) · 2023Article
- The identification of viral ribonucleotide reductase encoded by ORF23 and ORF141 genes and effect on CyHV-2 replication.Frontiers in microbiology · 2023Article
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- Emerging Mechanisms of GmBio · 2021Review
- Review
- Didox (3,4-dihydroxybenzohydroxamic acid) suppresses IL-33-induced cytokine production in primary mouse mast cells.Cellular immunology · 2017Article
- Human Cytomegalovirus Can Procure Deoxyribonucleotides for Viral DNA Replication in the Absence of Retinoblastoma Protein Phosphorylation.Journal of virology · 2016Article
- Anti-cytomegalovirus activity of the anthraquinone atanyl blue PRL.Antiviral research · 2015Article
- Ribonucleotide reductases: essential enzymes for bacterial life.Frontiers in cellular and infection microbiology · 2014Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Ganciclovir (GCV) is a deoxyguanosine analog that is effective in inhibiting human cytomegalovirus (HCMV) replication. In infected cells GCV is converted to GCV-triphosphate which competes with dGTP for incorporation into the growing DNA strand by the viral DNA polymerase. Incorporated GCV promotes chain termination as it is an inefficient substrate for elongation. Because viral DNA synthesis also relies on cellular ribonucleotide reductase (RR) to synthesize deoxynucleotides, RR inhibitors are predicted to inhibit HCMV replication. Moreover, as dGTP competes with GCV-triphosphate for incorporation, RR inhibitors may also synergize with GCV by reducing intracellular dGTP levels and there by promoting increased GCV-triphosphate utilization by DNA polymerase. To investigate potential of RR inhibitors as anti-HCMV agents both alone and in combination with GCV, HCMV-inhibitory activities of three RR inhibitors, hydroxyurea, didox, and trimidox, were determined. In both spread inhibition and yield reduction assays RR inhibitors had modest anti-HCMV activity with 50% inhibitory concentrations ranging from 36±1.7 to 221±52μM. However, all three showed significant synergy with GCV at concentrations below their 50% inhibitory and 50% toxic concentrations. These results suggest that combining GCV with relatively low doses of RR inhibitors could significantly potentiate the anti-HCMV activity of GCV in vivo and could improve clinical response to therapy.
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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 OpenQuestion graph.