ArticleCell reports2017
Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- The nucleoside analog CMX521 inhibits coronavirus RNA-dependent RNA polymerase via a two-pronged mechanism.bioRxiv : the preprint server for biology · 2026Article
- RNA virus polymerase-helicase coupling enables rapid elongation through duplex RNA.Cell reports · 2026Article
- Article
- Determination of Non-Cytotoxic Antiviral Concentrations of Phosphoric Acid Derivatives and Nucleotide Base Analogues In Vitro.Bulletin of experimental biology and medicine · 2025Article
- A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.Nucleic acids research · 2025Article
- Article
- Non-lytic spread of poliovirus requires the nonstructural protein 3CD.bioRxiv : the preprint server for biology · 2024Article
- A mutation-sensitive, multiplexed and amplification-free detection of nucleic acids by stretching single-molecule tandem hairpin probes.Nucleic acids research · 2023Article
- Interfering with nucleotide excision by the coronavirus 3'-to-5' exoribonuclease.Nucleic acids research · 2023Article
- The enterovirus genome can be translated in an IRES-independent manner that requires the initiation factors eIF2A/eIF2D.PLoS biology · 2023Article
- Interfering with nucleotide excision by the coronavirus 3'-to-5' exoribonuclease.bioRxiv : the preprint server for biology · 2022Article
- Druggable targets and therapeutic development for COVID-19.Frontiers in chemistry · 2022Review
- Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design.Nature reviews. Molecular cell biology · 2022Review
- Induced intra- and intermolecular template switching as a therapeutic mechanism against RNA viruses.Molecular cell · 2021Article
- Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective.eLife · 2021Article
- The nucleotide addition cycle of the SARS-CoV-2 polymerase.Cell reports · 2021Article
- Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit.The Journal of infectious diseases · 2021Article
- Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Residence time analysis of RNA polymerase transcription dynamics: A Bayesian sticky HMM approach.Biophysical journal · 2021Article
- Inhibition of SARS-CoV-2 polymerase by nucleotide analogs: a single molecule perspective.bioRxiv : the preprint server for biology · 2021Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
RNA viruses pose a threat to public health that is exacerbated by the dearth of antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) holds promise as a broad-spectrum, therapeutic target because of the conserved nature of the nucleotide-substrate-binding and catalytic sites. Conventional, quantitative, kinetic analysis of antiviral ribonucleotides monitors one or a few incorporation events. Here, we use a high-throughput magnetic tweezers platform to monitor the elongation dynamics of a prototypical RdRp over thousands of nucleotide-addition cycles in the absence and presence of a suite of nucleotide analog inhibitors. We observe multiple RdRp-RNA elongation complexes; only a subset of which are competent for analog utilization. Incorporation of a pyrazine-carboxamide nucleotide analog, T-1106, leads to RdRp backtracking. This analysis reveals a mechanism of action for this antiviral ribonucleotide that is corroborated by cellular studies. We propose that induced backtracking represents a distinct mechanistic class of antiviral ribonucleotides.
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