ArticleThe Journal of biological chemistry2020
Resistance to excision determines efficiency of hepatitis C virus RNA-dependent RNA polymerase inhibition by nucleotide analogs.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
9 citing papers in PubMed.
- The 5'-Isobutyryl Ester Prodrug of 4'-Thiouridine Inhibits SARS-CoV‑2 Replication in Culture and in a Syrian Hamster Infection Model.ACS omega · 2026Article
- 1'-Cyanocytidine-5'-isobutyryl is a potent SARS-CoV-2 inhibitor in culture and infected Syrian hamsters.Science advances · 2025Article
- Mechanism of Inhibition of the Active Triphosphate Form of 2'-α-Fluoro,2'-β-bromouridine against Yellow Fever Virus RNA-Dependent RNA Polymerase.ACS infectious diseases · 2025Article
- Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective.eLife · 2021Article
- Inhibition of SARS-CoV-2 polymerase by nucleotide analogs: a single molecule perspective.bioRxiv : the preprint server for biology · 2021Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- Mechanisms of inhibition of viral RNA replication by nucleotide analogs.The Enzymes · 2021Review
- Remdesivir Is Effective in Combating COVID-19 because It Is a Better Substrate than ATP for the Viral RNA-Dependent RNA Polymerase.iScience · 2020Article
- Rate-limiting pyrophosphate release by hepatitis C virus polymerase NS5B improves fidelity.The Journal of biological chemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
NS5B is the RNA-dependent RNA polymerase that catalyzes the replication of the hepatitis C virus genome. It is a major target for antiviral drugs including nucleoside analogs, such as the prodrugs mericitabine and sofosbuvir, which get metabolized to 2'-fluoro-2'C-methylcytidine-5'-triphosphate and 2'-fluoro-2'C-methyluridine-5'-triphosphate, respectively. These analogs act as chain terminators after they are incorporated during RNA synthesis. Recently, it has been shown that NS5B can efficiently remove chain terminators by a nucleotide-mediated excision reaction that rescues RNA synthesis. In this study, we use transient-state kinetics to understand the efficiency of inhibition for five nucleoside analogs. We show that CTP analogs are readily incorporated into a growing primer by NS5B but are also efficiently excised. In contrast, although UMP analogs are more slowly incorporated, the excision of UMP is slow and inefficient, and modifications to the 2'-carbon of the UTP ribose ring further decreased rates of excision to an undetectable level. Taken together, these data suggest that the clinical effectiveness of sofosbuvir is largely a function of being intractable to nucleotide-mediated excision compared with similar nucleoside analogs.
Indexed as
Identifiers
What OpenQuestion holds
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.