ArticleJournal of virology2020
Non-nucleoside Inhibitors of Zika Virus RNA-Dependent RNA Polymerase.
Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Synthesis of Novel Acetylene-Containing Phosphonates, Their Antiviral Activity, and Their Cytotoxicity to Different Cancer Cell Lines.Molecules (Basel, Switzerland) · 2026Article
- Antiviral Efficacy of Lignan Derivatives (-)-Asarinin and Sesamin Against Foot-and-Mouth Disease Virus by Targeting RNA-Dependent RNA Polymerase (3DVeterinary sciences · 2025Article
- Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals.Journal of medicinal chemistry · 2025Article
- Effects of the fatty acid synthase inhibitors triclosan and lapatinib on dengue virus and Zika virus infection.Scientific reports · 2025Article
- Dengue Virus Inhibitors as Potential Broad-Spectrum Flavivirus Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Exploring Echinacea angustifolia for anti-viral compounds against Zika virus RNA-dependent RNA polymerase: a computational study.Scientific reports · 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
- Binding of Nucleotide Inhibitors to the NS5 RdRp of the ZIKA Virus in the Replication Initiation State.Current medicinal chemistry · 2025Article
- Non-Nucleoside Lycorine-Based Analogs as Potential DENV/ZIKV NS5 Dual Inhibitors: Structure-Based Virtual Screening and Chemoinformatic Analysis.Metabolites · 2024Article
- The Potential of Usnic-Acid-Based Thiazolo-Thiophenes as Inhibitors of the Main Protease of SARS-CoV-2 Viruses.Viruses · 2024Article
- Recent advances in the study of zika virus structure, drug targets, and inhibitors.Frontiers in pharmacology · 2024Review
- Antiviral Activity of Flavonoids from Geopropolis of the Brazilian Jandaira Bee against Zika and Dengue Viruses.Pharmaceutics · 2023Article
- Article
- Structures of active Hantaan virus polymerase uncover the mechanisms of Hantaviridae genome replication.Nature communications · 2023Article
- Flavivirus nonstructural proteins and replication complexes as antiviral drug targets.Current opinion in virology · 2023Review
- Splicing factor SF3B3, a NS5-binding protein, restricts ZIKV infection by targeting GCH1.Virologica Sinica · 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
- Small-Molecule Inhibitor of Flaviviral NS3-NS5 Interaction with Broad-Spectrum Activity and EfficacymBio · 2023Article
- Non-Nucleoside Inhibitors Decrease Foot-and-Mouth Disease Virus Replication by Blocking the Viral 3DViruses · 2022Article
- Discovery of New Zika Protease and Polymerase Inhibitors through the Open Science Collaboration Project OpenZika.Journal of chemical information and modeling · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zika virus (ZIKV) remains a potentially significant public health concern because it can cause teratogenic effects, such as microcephaly in newborns and neurological disease, like Guillain-Barré syndrome. Together with efforts to develop a vaccine, the discovery of antiviral molecules is important to control ZIKV infections and to prevent its most severe symptoms. Here, we report the development of small nonnucleoside inhibitors (NNIs) of ZIKV RNA-dependent RNA polymerase (RdRp) activity. These NNIs target an allosteric pocket (N pocket) located next to a putative hinge region between the thumb and the palm subdomains that was originally described for dengue virus (DENV) RdRp. We first tested the activity of DENV RdRp N-pocket inhibitors against ZIKV RdRp, introduced chemical modifications into these molecules, and assessed their potency using both enzymatic and cell-based assays. The most potent compound had a 50% inhibitory concentration value of 7.3 μM and inhibited ZIKV replication in a cell-based assay with a 50% effective concentration value of 24.3 μM. Importantly, we report four high-resolution crystal structures detailing how these NNIs insert into the N pocket of ZIKV RdRp. Our observations point to subtle differences in the size, shape, chemical environment, and hydration of the N pocket from ZIKV RdRp from those of the N pocket from DENV RdRp that are crucial for the design of improved antiviral inhibitors with activity against ZIKV.
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Registered trials
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.