ArticleThe Journal of antimicrobial chemotherapy2017
Purification of Zika virus RNA-dependent RNA polymerase and its use to identify small-molecule Zika inhibitors.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- Positive-Strand RNA Viral RdRps: From Structure Conservation and Activity Assay to Drug Development.Molecules (Basel, Switzerland) · 2026Review
- Article
- Mechanism of Inhibition of the Active Triphosphate Form of 2'-α-Fluoro,2'-β-bromouridine against Yellow Fever Virus RNA-Dependent RNA Polymerase.ACS infectious diseases · 2025Article
- Aryl benzoyl hydrazide derivatives as potent inhibitors of the NS2B-NS3 protease and RNA-dependent RNA polymerase of the zika virus.In silico pharmacology · 2025Article
- Recent advances in the study of zika virus structure, drug targets, and inhibitors.Frontiers in pharmacology · 2024Review
- Repurposing of drugs against methyltransferase as potential Zika virus therapies.Scientific reports · 2023Article
- Antiviral effects of the fused tricyclic derivatives of indoline and imidazolidinone on ZIKV infection and RdRp activities of ZIKV and DENV.Virus research · 2023Article
- Kill or corrupt: Mechanisms of action and drug-resistance of nucleotide analogues against SARS-CoV-2.Antiviral research · 2023Review
- Inhibition of Viral RNA-Dependent RNA Polymerases by Nucleoside Inhibitors: An Illustration of the Unity and Diversity of Mechanisms.International journal of molecular sciences · 2022Review
- A review on structural genomics approach applied for drug discovery against three vector-borne viral diseases: Dengue, Chikungunya and Zika.Virus genes · 2022Review
- Chalcones from Angelica keiskei (ashitaba) inhibit key Zika virus replication proteins.Bioorganic chemistry · 2022Article
- Mutation in the RNA-Dependent RNA Polymerase of a Symbiotic Virus Is Associated With the Adaptability of the Viral Host.Frontiers in microbiology · 2022Article
- Identification of 6ω-cyclohexyl-2-(phenylamino carbonylmethylthio)pyrimidin-4(3Frontiers in chemistry · 2022Article
- Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection.Frontiers of medicine · 2021Review
- Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro.International journal of molecular sciences · 2021Article
- Recent advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses.RSC medicinal chemistry · 2021Review
- Identification and Characterization of Zika Virus NS5 Methyltransferase Inhibitors.Frontiers in cellular and infection microbiology · 2021Article
- Within and Beyond the Nucleotide Addition Cycle of Viral RNA-dependent RNA Polymerases.Frontiers in molecular biosciences · 2021Article
- Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge.Molecules (Basel, Switzerland) · 2020Review
- Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach.International journal of biological macromolecules · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Background: The viral RNA-dependent RNA polymerase (RdRp) enzymes of the Flaviviridae family are essential for viral replication and are logically important targets for development of antiviral therapeutic agents. Zika virus (ZIKV) is a rapidly re-emerging human pathogen for which no vaccine or antiviral agent is currently available. Methods: To facilitate development of ZIKV RdRp inhibitors, we have established an RdRp assay using purified recombinant ZIKV NS5 polymerase. Results: We have shown that both the hepatitis C virus (HCV) nucleoside inhibitor sofosbuvir triphosphate and a pyridoxine-derived non-nucleoside small-molecule inhibitor, DMB213, can act against ZIKV RdRp activity at IC 50 s of 7.3 and 5.2 μM, respectively, in RNA synthesis reactions catalysed by recombinant ZIKV NS5 polymerase. Cell-based assays confirmed the anti-ZIKV activity of sofosbuvir and DMB213 with 50% effective concentrations (EC 50 s) of 8.3 and 4.6 μM, respectively. Control studies showed that DMB213 did not inhibit recombinant HIV-1 reverse transcriptase and showed only very weak inhibition of HIV-1 integrase strand-transfer activity. The S604T substitution in motif B of the ZIKV RdRp, which corresponds to the S282T substitution in motif B of HCV RdRp, which confers resistance to nucleotide inhibitors, also conferred resistance to sofosbuvir triphosphate, but not to DMB213. Enzyme assays showed that DMB213 appears to be competitive with natural nucleoside triphosphate (NTP) substrates. Conclusions: Recombinant ZIKV RdRp assays can be useful tools for the screening of both nucleos(t)ide compounds and non-nucleotide metal ion-chelating agents that interfere with ZIKV replication.
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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.