ArticleAntiviral research2011
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
Article in Antiviral research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- A Multi-Model Machine Learning Framework for Identifying Raloxifene as a Novel RNA Polymerase Inhibitor from FDA-Approved Drugs.Current issues in molecular biology · 2025Article
- The multiple roles of viral 3DVirulence · 2024Review
- Molecular modeling of some commercially available antiviral drugs and their derivatives against SARS-CoV-2 infection.Narra J · 2024Article
- Molecular modelling and simulation techniques to investigate the effects of fungal metabolites on the SARS-CoV-2 RdRp protein inhibition.Journal of King Saud University. Science · 2022Article
- In Silico Molecular Dynamics of Griseofulvin and Its Derivatives Revealed Potential Therapeutic Applications for COVID-19.International journal of molecular sciences · 2022Article
- Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches.Journal of biomolecular structure & dynamics · 2022Article
- Application of Networking Approaches to Assess the Chemical Diversity, Biogeography, and Pharmaceutical Potential of Verongiida Natural Products.Marine drugs · 2021Article
- Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme.Science (New York, N.Y.) · 2021Article
- RNA-dependent RNA polymerase: Structure, mechanism, and drug discovery for COVID-19.Biochemical and biophysical research communications · 2021Review
- RNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery.SLAS discovery : advancing life sciences R & D · 2020Review
- Development of FRET-based high-throughput screening for viral RNase III inhibitors.Molecular plant pathology · 2020Article
- Development of a fluorescence-based method for the rapid determination of Zika virus polymerase activity and the screening of antiviral drugs.Scientific reports · 2019Article
- Targeting the Viral Polymerase of Diarrhea-Causing Viruses as a Strategy to Develop a Single Broad-Spectrum Antiviral Therapy.Viruses · 2019Review
- Structure(s), function(s), and inhibition of the RNA-dependent RNA polymerase of noroviruses.Virus research · 2017Review
- An in vitro fluorescence based study of initiation of RNA synthesis by influenza B polymerase.Nucleic acids research · 2017Article
- Allosteric inhibitors of Coxsackie virus A24 RNA polymerase.Bioorganic & medicinal chemistry · 2016Article
- Sequence specificity for uridylylation of the viral peptide linked to the genome (VPg) of enteroviruses.Virology · 2015Article
- The RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family.PLoS pathogens · 2015Article
- Article
- Nonnucleoside inhibitors of norovirus RNA polymerase: scaffolds for rational drug design.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Viral RNA-dependent RNA polymerase (RdRP) enzymes are essential for the replication of positive-strand RNA viruses and established targets for the development of selective antiviral therapeutics. In this work we have carried out a high-throughput screen of 154,267 compounds to identify poliovirus polymerase inhibitors using a fluorescence based RNA elongation assay. Screening and subsequent validation experiments using kinetic methods and RNA product analysis resulted in the identification of seven inhibitors that affect the RNA binding, initiation, or elongation activity of the polymerase. X-ray crystallography data show clear density for five of the compounds in the active site of the poliovirus polymerase elongation complex. The inhibitors occupy the NTP binding site by stacking on the priming nucleotide and interacting with the templating base, yet competition studies show fairly weak IC50 values in the low μM range. A comparison with nucleotide bound structures suggests that weak binding is likely due to the lack of a triphosphate group on the inhibitors. Consequently, the inhibitors are primarily effective at blocking polymerase initiation and do not effectively compete with NTP binding during processive elongation. These findings are discussed in the context of the polymerase elongation complex structure and allosteric control of the viral RdRP catalytic cycle.
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