ArticlemBio2021
Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides.
Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 31 citations in OpenAlex.
- Copy-back RNA synthesis by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.Science advances · 2026Article
- Template switching by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.bioRxiv : the preprint server for biology · 2025Article
- A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.Nucleic acids research · 2025Article
- RedefiningMolecular therapy. Nucleic acids · 2025Article
- Biochemical characterization of naturally occurring mutations in SARS-CoV-2 RNA-dependent RNA polymerase.Protein science : a publication of the Protein Society · 2024Article
- Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.NPJ science of food · 2024Review
- Studying the intersection of nucleoside modifications and SARS-CoV-2 RNA-dependent RNA transcription using an in vitro reconstituted system.Methods in enzymology · 2024Article
- Fierce poison to others: the phenomenon of bacterial dependence on antibiotics.Journal of biomedical science · 2023Review
- Viral target and metabolism-based rationale for combined use of recently authorized small molecule COVID-19 medicines: Molnupiravir, nirmatrelvir, and remdesivir.Fundamental & clinical pharmacology · 2023Review
- Effects of natural RNA modifications on the activity of SARS-CoV-2 RNA-dependent RNA polymerase.The FEBS journal · 2023Article
- SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.Signal transduction and targeted therapy · 2022Article
- Identification of Polyphenol Derivatives as Novel SARS-CoV-2 and DENV Non-Nucleoside RdRp Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- COVID-19 metabolism: Mechanisms and therapeutic targets.MedComm · 2022Review
- Vitamin C and its therapeutic potential in the management of COVID19.Clinical nutrition ESPEN · 2022Review
- Composition of naturally occurring compounds decreases activity of Omicron and SARS-CoV-2 RdRp complex.European journal of microbiology & immunology · 2022Article
- Going Retro, Going Viral: Experiences and Lessons in Drug Discovery from COVID-19.Molecules (Basel, Switzerland) · 2022Article
- Promising Assays for Examining a Putative Role of Ribosomal Heterogeneity in COVID-19 Susceptibility and Severity.Life (Basel, Switzerland) · 2022Review
- Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition.Molecules (Basel, Switzerland) · 2021Article
- Remdesivir: Quo vadis?Biochemical pharmacology · 2021Review
- NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain.Nucleic acids research · 2021Article
Corrections and comments
- Update of
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The catalytic subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) Nsp12 has a unique nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain that transfers nucleoside monophosphates to the Nsp9 protein and the nascent RNA. The NiRAN and RdRp modules form a dynamic interface distant from their catalytic sites, and both activities are essential for viral replication. We report that codon-optimized (for the pause-free translation in bacterial cells) Nsp12 exists in an inactive state in which NiRAN-RdRp interactions are broken, whereas translation by slow ribosomes and incubation with accessory Nsp7/8 subunits or nucleoside triphosphates (NTPs) partially rescue RdRp activity. Our data show that adenosine and remdesivir triphosphates promote the synthesis of A-less RNAs, as does ppGpp, while amino acid substitutions at the NiRAN-RdRp interface augment activation, suggesting that ligand binding to the NiRAN catalytic site modulates RdRp activity. The existence of allosterically linked nucleotidyl transferase sites that utilize the same substrates has important implications for understanding the mechanism of SARS-CoV-2 replication and the design of its inhibitors.
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.