ArticleThe FEBS journal2023
Effects of natural RNA modifications on the activity of SARS-CoV-2 RNA-dependent RNA polymerase.
Article in The FEBS journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Copy-back RNA synthesis by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.Science advances · 2026Article
- Positive-Strand RNA Viral RdRps: From Structure Conservation and Activity Assay to Drug Development.Molecules (Basel, Switzerland) · 2026Review
- Template switching by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.bioRxiv : the preprint server for biology · 2025Article
- Impact of an oxidative RNA lesion on in vitro replication catalyzed by SARS-CoV-2 RNA-dependent RNA polymerase.The Journal of biological chemistry · 2025Article
- RedefiningMolecular therapy. Nucleic acids · 2025Article
- Adenosine modifications impede SARS-CoV-2 RNA-dependent RNA transcription.RNA (New York, N.Y.) · 2024Article
- Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine.iScience · 2024Article
- Studying the intersection of nucleoside modifications and SARS-CoV-2 RNA-dependent RNA transcription using an in vitro reconstituted system.Methods in enzymology · 2024Article
- Phenotypic Test of Benzo[4,5]imidazo[1,2-c]pyrimidinone-Based Nucleoside and Non-Nucleoside Derivatives against DNA and RNA Viruses, Including Coronaviruses.International journal of molecular sciences · 2023Article
- Effects of natural polymorphisms in SARS-CoV-2 RNA-dependent RNA polymerase on its activity and sensitivity to inhibitors in vitro.Biochimie · 2023Article
- Nucleoside Analogs That Inhibit SARS-CoV-2 Replication by Blocking Interaction of Virus Polymerase with RNA.International journal of molecular sciences · 2023Article
- Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase.Computational and structural biotechnology journal · 2023Review
- The regulation of antiviral innate immunity through non-mFrontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA-dependent RNA polymerase (RdRp) plays a key role in the replication of RNA viruses, including SARS-CoV-2. Processive RNA synthesis by RdRp is crucial for successful genome replication and expression, especially in the case of very long coronaviral genomes. Here, we analysed the activity of SARS-CoV-2 RdRp (the nsp12-nsp7-nsp8 complex) on synthetic primer-templates of various structures, including substrates with mismatched primers or template RNA modifications. It has been shown that RdRp cannot efficiently extend RNA primers containing mismatches and has no intrinsic RNA cleavage activity to remove the primer 3'-end, thus necessitating the action of exoribonuclease for proofreading. Similar to DNA-dependent RNA polymerases, RdRp can perform processive pyrophosphorolysis of the nascent RNA product but this reaction is also blocked in the presence of mismatches. Furthermore, we have demonstrated that several natural post-transcriptional modifications in the RNA template, which do not prevent complementary interactions (N6-methyladenosine, 5-methylcytosine, inosine and pseudouridine), do not change RdRp processivity. At the same time, certain modifications of RNA bases and ribose residues strongly block RNA synthesis, either prior to nucleotide incorporation (3-methyluridine and 1-methylguanosine) or immediately after it (2'-O-methylation). The results demonstrate that the activity of SARS-CoV-2 RdRp can be strongly inhibited by common modifications of the RNA template suggesting a way to design novel antiviral compounds.
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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.