ReviewAntiviral chemistry & chemotherapy
Current and future use of nucleo(s)tide prodrugs in the treatment of hepatitis C virus infection.
Review in Antiviral chemistry & chemotherapy. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis.BMC infectious diseases · 2021Pooled it
- Improving stereoselectivity of phosphotriesterase (PTE) for kinetic resolution of chiral phosphates.Frontiers in bioengineering and biotechnology · 2024Article
- Prodrugs of Nucleoside 5'-Monophosphate Analogues: Overview of the Recent Literature Concerning their Synthesis and Applications.Current medicinal chemistry · 2023Review
- An update on inhibitors targeting RNA-dependent RNA polymerase for COVID-19 treatment: Promises and challenges.Biochemical pharmacology · 2022Review
- Bisubstrate Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 Nsp14 Methyltransferase.ACS medicinal chemistry letters · 2022Article
- Sofosbuvir-based direct-acting antivirals and changes in cholesterol and low density lipoprotein-cholesterol.Scientific reports · 2022Article
- Prodrugs of pyrophosphates and bisphosphonates: disguising phosphorus oxyanions.RSC medicinal chemistry · 2022Review
- A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase.Nature communications · 2022Article
- SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development.PLoS pathogens · 2021Review
- Synthesis and anti-HCV activity of β-d-2'-deoxy-2'-α-chloro-2'-β-fluoro and β-d-2'-deoxy-2'-α-bromo-2'-β-fluoro nucleosides and their phosphoramidate prodrugs.Bioorganic & medicinal chemistry · 2019Article
- Targeting HCV polymerase: a structural and dynamic perspective into the mechanism of selective covalent inhibition.RSC advances · 2018Article
- Discovery of 3-Amino-2-Hydroxypropoxyisoflavone Derivatives as Potential Anti-HCV Agents.Molecules (Basel, Switzerland) · 2018Article
- Targeting viral genome synthesis as broad-spectrum approach against RNA virus infections.Antiviral chemistry & chemotherapyReview
Corrections and comments
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Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This review describes the current state of discovery of past most important nucleoside and nucleotide prodrugs in the treatment of hepatitis C virus infection as well as future potential drugs currently in discovery or clinical evaluation. I highlight first generation landmark prodrug compounds which have been the foundations of incremental improvements toward the discovery and approval milestone of Sofosbuvir. Sofosbuvir is the first nucleotide prodrug marketed for hepatitis C virus treatment and the backbone of current combination therapies. Since this approval, new nucleotide prodrugs using the same design of Sofosbuvir McGuigan prodrug have emerged, some of them progressing through advanced clinical trials and may become available as new incremental alternative hepatitis C virus treatments in the future. Although since Sofosbuvir success, only minimal design efforts have been invested in finding better liver targeted prodrugs, a few novel prodrugs are being studied and their different modes of activation may prove beneficial over the heart/liver targeting ratio to reduce potential drug-drug interaction in combination therapies and yield safer treatment to patients. Prodrugs have long been avoided as much as possible in the past by development teams due to their metabolism and kinetic characterization complexity, but with their current success in hepatitis C virus treatment, and the knowledge gained in this endeavor, should become a first choice in future tissue targeting drug discovery programs beyond the particular case of nucleos(t)ide analogs.
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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.