ArticleNucleic acids research2017
NS3 helicase from dengue virus specifically recognizes viral RNA sequence to ensure optimal replication.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 79 citations in OpenAlex.
- Transcriptome signature for host directed antiviral reprogramming by Nimba & Triphala in macrophage Dengue virus infection models.Scientific reports · 2026Article
- Allosteric Regulation of RNA Affinity by Motif V-VI Coupling in West Nile Virus NS3 Helicase.Proteins · 2026Article
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- Design of a novel epitope-based tetravalent subunit vaccine against dengue virus: An immunoinformatic approach.PloS one · 2026Article
- In Silico-Based Identification of Natural Inhibitors from Traditionally Used Medicinal Plants that can Inhibit Dengue Infection.Molecular biotechnology · 2025Article
- An integrated proteomics approach identifies phosphorylation sites on viral and host proteins that regulate West Nile virus infection.Cell reports · 2025Article
- Development of New Live-Attenuated Vaccine Candidates Lacking Antibody-Dependent Enhancement (ADE) Against Dengue.Vaccines · 2025Review
- Ivermectin Inhibits Zika Virus Replication in Vitro But Does Not Prevent Zika Virus Infection in Rhesus Macaques (Macaca mulatta).The American journal of tropical medicine and hygiene · 2025Article
- Dengue virus: pathogenesis and potential for small molecule inhibitors.Bioscience reports · 2024Review
- Orthoflaviviral Inhibitors in Clinical Trials, Preclinical In Vivo Efficacy Targeting NS2B-NS3 and Cellular Antiviral Activity via Competitive Protease Inhibition.Molecules (Basel, Switzerland) · 2024Review
- Generalized open-source workflows for atomistic molecular dynamics simulations of viral helicases.GigaScience · 2024Article
- Impact of bound ssRNA length on allostery in the Dengue Virus NS3 helicase.Nucleic acids research · 2023Article
- Structure-first identification of RNA elements that regulate dengue virus genome architecture and replication.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Flavivirus nonstructural proteins and replication complexes as antiviral drug targets.Current opinion in virology · 2023Review
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- Liver immunopathogenesis in fatal cases of dengue in children: detection of viral antigen, cytokine profile and inflammatory mediators.Frontiers in immunology · 2023Article
- Immunopathology of Renal Tissue in Fatal Cases of Dengue in Children.Pathogens (Basel, Switzerland) · 2022Article
- Immune-Mediated Pathogenesis in Dengue Virus Infection.Viruses · 2022Review
- Seeking heterocyclic scaffolds as antivirals against dengue virus.European journal of medicinal chemistry · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein-RNA interactions within the flavivirus replication complex (RC) are not fully understood. Our structure of dengue virus NS3 adenosine triphosphatase (ATPase)/helicase bound to the conserved 5' genomic RNA 5'-AGUUGUUAGUCU-3' reveals that D290 and R538 make specific interactions with G2 and G5 bases respectively. We show that single-stranded 12-mer RNA stimulates ATPase activity of NS3, however the presence of G2 and G5 leads to significantly higher activation. D290 is adjacent to the DEXH motif found in SF2 helicases like NS3 and interacts with R387, forming a molecular switch that activates the ATPase site upon RNA binding. Our structure guided mutagenesis revealed that disruption of D290-R387 interaction increases basal ATPase activity presumably as a result of higher conformational flexibility of the ATPase active site. Mutational studies also showed R538 plays a critical role in RNA interactions affecting translocation of viral RNA through dynamic interactions with bases at positions 4 and 5 of the ssRNA. Restriction of backbone flexibility around R538 through mutation of G540 to proline abolishes virus replication, indicating conformational flexibility around residue R538 is necessary for RNA translocation. The functionally critical sequence-specific contacts in NS3 RNA binding groove in subdomain III reveals potentially novel allosteric anti-viral drug targets.
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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.