ArticleAntimicrobial agents and chemotherapy2016
Potency and Stereoselectivity of Cyclopropavir Triphosphate Action on Human Cytomegalovirus DNA Polymerase.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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Who cites it
11 citing papers in PubMed, 16 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
- Anti-CMV therapy, what next? A systematic review.Frontiers in microbiology · 2023Review
- 40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?International journal of molecular sciences · 2022Review
- Pentostatin antagonizes the antiviral activity of MBX-2168 by inhibiting the biosynthesis of the active compound.Antiviral research · 2021Article
- Article
- Antiviral Drugs Against Herpesviruses.Advances in experimental medicine and biology · 2021Article
- Filociclovir Is a PotentAntimicrobial agents and chemotherapy · 2020Article
- Synthesis of New Imidazopyridine Nucleoside Derivatives Designed as Maribavir Analogues.Molecules (Basel, Switzerland) · 2020Article
- Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy.Current hematologic malignancy reports · 2020Review
- Biosynthesis and half-life of MBX-2168-triphosphate in herpes virus-infected cells.Antiviral research · 2020Article
- Activation of 6-Alkoxy-Substituted Methylenecyclopropane Nucleoside Analogs Requires Enzymatic Modification by Adenosine Deaminase-Like Protein 1.Antimicrobial agents and chemotherapy · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Cyclopropavir (CPV) is a promising antiviral drug against human cytomegalovirus (HCMV). As with ganciclovir (GCV), the current standard for HCMV treatment, activation of CPV requires multiple steps of phosphorylation and is enantioselective. We hypothesized that the resulting CPV triphosphate (CPV-TP) would stereoselectively target HCMV DNA polymerase and terminate DNA synthesis. To test this hypothesis, we synthesized both enantiomers of CPV-TP [(+) and (-)] and investigated their action on HCMV polymerase. Both enantiomers inhibited HCMV polymerase competitively with dGTP, with (+)-CPV-TP exhibiting a more than 20-fold lower apparent Ki than (-)-CPV-TP. Moreover, (+)-CPV-TP was a more potent inhibitor than GCV-TP. (+)-CPV-TP also exhibited substantially lower apparent Km and somewhat higher apparent kcat values than (-)-CPV-TP and GCV-TP for incorporation into DNA by the viral polymerase. As is the case for GCV-TP, both CPV-TP enantiomers behaved as nonobligate chain terminators, with the polymerase terminating DNA synthesis after incorporation of one additional nucleotide. These results elucidate how CPV-TP acts on HCMV DNA polymerase and help explain why CPV is more potent against HCMV replication than GCV.
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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.