About: Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers

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About: Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers
Creator	Arnold, Jamie Cameron, Craig Dekker, Nynke Depken, Martin Dulin, David Harki, Daniel Lee, Cheri Oh, Hyung-Suk Perkins, Angela Van Laar, Theo
Source	Elsevier; Medline; PMC
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.
has issue date	2017-10-24(xsd:dateTime)
bibo:doi	10.1016/j.celrep.2017.10.005
bibo:pmid	29069588
has license	cc-by-nc-nd
sha1sum (hex)	650c04938724d08709151733994c22ddd00b68aa
schema:url	https://doi.org/10.1016/j.celrep.2017.10.005
resource representing a document's title	Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers
has PubMed Central identifier	PMC5670035
has PubMed identifier	29069588
schema:publication	Cell Rep
resource representing a document's body	covid:650c04938724d08709151733994c22ddd00b68aa#body_text
is schema:about of	named entity 'RNA-DEPENDENT RNA POLYMERASE' named entity 'SIGNATURES' named entity 'HIGH' named entity 'SUPPLEMENTAL' named entity 'INFORMATION' named entity 'NUCLEOTIDE ANALOG' named entity 'MAGNETIC TWEEZERS' named entity 'THROUGHPUT' named entity 'REVEALED' named entity 'USING' named entity 'RNA' named entity 'ATP' named entity 'nucleotide addition' named entity 'BSIC' named entity 'ATP' named entity 'PCR' named entity 'dwell-time' named entity 'nutrient' named entity 'uridine' named entity 'RNA synthesis' named entity 'hybridized' named entity 'Dulbecco' named entity 'probability' named entity 'F-12' named entity 'molecule' named entity 'Qiagen' named entity 'hybridization' named entity 'probability' named entity 'primers' named entity 'dwell-time' named entity 'template strand' named entity 'dwell-time' named entity 'CCL-2' named entity 'Denaturing' named entity 'nucleotide' named entity 'Prof.' named entity 'RNA' named entity 'dsRNA' named entity 'Promega' named entity 'rate-limiting step' named entity 'ATCC' named entity 'Plasmid' named entity 'probability' named entity 'single-molecule studies' named entity 'probability' named entity 'ssRNA' named entity 'ATP' named entity 'nucleotide addition' named entity 'nucleotide' named entity 'T7 RNA polymerase' named entity 'nucleotide addition' named entity 'exponentially distributed' named entity 'primer' named entity 'American type culture collection' named entity 'Fetal' named entity 'RNA molecules' named entity 'RNA' named entity 'dwell-time' named entity 'Penicillin' named entity 'incubated' named entity 'template strand' named entity 'RNA' named entity 'Bovine' named entity 'Serum' named entity 'template strand' named entity 'hybridized' named entity 'probability' named entity 'dwell-time' named entity 'nucleotide addition' named entity 'primer' named entity 'nucleotide' named entity 'RNA'

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