ArticleAntimicrobial agents and chemotherapy2011
Cyclopropavir inhibits the normal function of the human cytomegalovirus UL97 kinase.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01433835 (Safety and Pharmacokinetics of Single Oral Doses of MBX-400 in Healthy Volunteers), which is not on this map. Cited by 26 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.
Safety and Pharmacokinetics of Single Oral Doses of MBX-400 in Healthy Volunteers
Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Phase Ib Trial To Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of Filociclovir (MBX-400, Cyclopropavir) in Healthy Volunteers.Antimicrobial agents and chemotherapy · 2019Trial
- Article
- Human cytomegalovirus: pathogenesis, prevention, and treatment.Molecular biomedicine · 2024Review
- Anti-CMV therapy, what next? A systematic review.Frontiers in microbiology · 2023Review
- Filociclovir Is an Active Antiviral Agent against Ocular Adenovirus Isolates In Vitro and in the Ad5/NZW Rabbit Ocular Model.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Antiviral Drugs Against Herpesviruses.Advances in experimental medicine and biology · 2021Article
- The Cytomegalovirus Protein Kinase pUL97:Host Interactions, Regulatory Mechanisms and Antiviral Drug Targeting.Microorganisms · 2020Review
- Advances in the genotypic diagnosis of cytomegalovirus antiviral drug resistance.Antiviral research · 2020Review
- Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy.Current hematologic malignancy reports · 2020Review
- Advances in the Development of Therapeutics for Cytomegalovirus Infections.The Journal of infectious diseases · 2020Review
- Novel Therapeutics for Epstein⁻Barr Virus.Molecules (Basel, Switzerland) · 2019Review
- Comparison of three dimensional synergistic analyses of percentage versus logarithmic data in antiviral studies.Antiviral research · 2017Article
- Distribution and effects of amino acid changes in drug-resistant α and β herpesviruses DNA polymerase.Nucleic acids research · 2016Review
- Human cytomegalovirus and transplantation: drug development and regulatory issues.Journal of virus eradication · 2016Article
- Potency and Stereoselectivity of Cyclopropavir Triphosphate Action on Human Cytomegalovirus DNA Polymerase.Antimicrobial agents and chemotherapy · 2016Article
- The development of new therapies for human herpesvirus 6.Current opinion in virology · 2014Review
- β-l-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (l-BHDU) prevents varicella-zoster virus replication in a SCID-Hu mouse model and does not interfere with 5-fluorouracil catabolism.Antiviral research · 2014Article
- Cytomegalovirus infection in liver transplant recipients: updates on clinical management.World journal of gastroenterology · 2014Review
- Retinazone inhibits certain blood-borne human viruses including Ebola virus Zaire.Antiviral chemistry & chemotherapy · 2014Article
- Genomic and functional characteristics of human cytomegalovirus revealed by next-generation sequencing.Viruses · 2014Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Cyclopropavir (CPV) is active against human cytomegalovirus (CMV), as well as both variants of human herpesvirus 6 and human herpesvirus 8. The mechanism of action of CPV against CMV is similar to that of ganciclovir (GCV) in that it is phosphorylated initially by the CMV UL97 kinase, resulting in inhibition of viral DNA synthesis. Resistance to CPV maps to the UL97 kinase but is associated primarily with H520Q mutations and thus retains good antiviral activity against most GCV-resistant isolates. An examination of CMV-infected cultures treated with CPV revealed unusual cell morphology typically associated with the absence of UL97 kinase activity. A surrogate assay for UL97 kinase activity confirmed that CPV inhibited the activity of this enzyme and that its action was similar to the inhibition seen with maribavir (MBV) in this assay. Combination studies using real-time PCR indicated that, like MBV, CPV also antagonized the efficacy of GCV and were consistent with the observed inhibition of the UL97 kinase. Deep sequencing of CPV-resistant laboratory isolates identified a frameshift mutation in UL27, presumably to compensate for a loss of UL97 enzymatic activity. We conclude that the mechanism of action of CPV against CMV is complex and involves both the inhibition of DNA synthesis and the inhibition of the normal activity of the UL97 kinase.
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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.