ArticleThe Journal of biological chemistry2015
The C-terminal 50 amino acid residues of dengue NS3 protein are important for NS3-NS5 interaction and viral replication.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 140 citations in OpenAlex.
- NS5 polymerase stimulates RNA duplex unwinding by the Orthoflavivirus NS3 helicase.The Journal of biological chemistry · 2026Article
- An orthoflavivirus inhibitor targeting multifunctional NS2A protein, a previously unidentified target.PLoS pathogens · 2026Article
- Unwinding of an RNA duplex by the Orthoflavivirus NS3 helicase requires translocation beyond the displaced strand and is stimulated by the NS5 RdRp.bioRxiv : the preprint server for biology · 2026Article
- Use of the Split Luciferase Complementation Assay to Identify Novel Small Molecules That Disrupt Essential Protein-Protein Interactions of Viruses.Biomolecules · 2025Article
- Meeting report: 38th international conference on antiviral research in Las Vegas, United States of America, March 17-21, 2025.Antiviral research · 2025Article
- New Pyridobenothiazolone Derivatives Display Nanomolar Pan-Serotype Anti-Dengue Virus Activity.ChemMedChem · 2025Article
- Development of New Live-Attenuated Vaccine Candidates Lacking Antibody-Dependent Enhancement (ADE) Against Dengue.Vaccines · 2025Review
- New dengue virus inhibitors targeting NS3-NS5 interaction identified byFrontiers in microbiology · 2025Article
- The interaction of Orthoflavivirus nonstructural proteins 3 and 5 with human fatty acid synthase.PloS one · 2025Article
- West Nile virus - a re-emerging global threat: recent advances in vaccines and drug discovery.Frontiers in cellular and infection microbiology · 2025Review
- West Nile virus unmasked: from gene variability to future challenges.Frontiers in cellular and infection microbiology · 2025Review
- Membrane Retention of West Nile Virus NS5 Depends on NS1 or NS3 for Enzymatic Activity.Viruses · 2024Article
- Serotype-Specific Regulation of Dengue Virus NS5 Protein Subcellular Localization.ACS infectious diseases · 2024Article
- A jingmenvirus RNA-dependent RNA polymerase structurally resembles the flavivirus counterpart but with different features at the initiation phase.Nucleic acids research · 2024Article
- Residue K28 of Zika Virus NS5 Protein Is Implicated in Virus Replication and Antagonism of STAT2.Microorganisms · 2024Article
- Article
- Deciphering the interaction surface between the West Nile virus NS3 and NS5 proteins.Access microbiology · 2024Article
- LGP2 directly interacts with flavivirus NS5 RNA-dependent RNA polymerase and downregulates its pre-elongation activities.PLoS pathogens · 2023Article
- Small-Molecule Inhibitor of Flaviviral NS3-NS5 Interaction with Broad-Spectrum Activity and EfficacymBio · 2023Article
- Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue virus multifunctional proteins NS3 protease/helicase and NS5 methyltransferase/RNA-dependent RNA polymerase form part of the viral replication complex and are involved in viral RNA genome synthesis, methylation of the 5'-cap of viral genome, and polyprotein processing among other activities. Previous studies have shown that NS5 residue Lys-330 is required for interaction between NS3 and NS5. Here, we show by competitive NS3-NS5 interaction ELISA that the NS3 peptide spanning residues 566-585 disrupts NS3-NS5 interaction but not the null-peptide bearing the N570A mutation. Small angle x-ray scattering study on NS3(172-618) helicase and covalently linked NS3(172-618)-NS5(320-341) reveals a rigid and compact formation of the latter, indicating that peptide NS5(320-341) engages in specific and discrete interaction with NS3. Significantly, NS3:Asn-570 to alanine mutation introduced into an infectious DENV2 cDNA clone did not yield detectable virus by plaque assay even though intracellular double-stranded RNA was detected by immunofluorescence. Detection of increased negative-strand RNA synthesis by real time RT-PCR for the NS3:N570A mutant suggests that NS3-NS5 interaction plays an important role in the balanced synthesis of positive- and negative-strand RNA for robust viral replication. Dengue virus infection has become a global concern, and the lack of safe vaccines or antiviral treatments urgently needs to be addressed. NS3 and NS5 are highly conserved among the four serotypes, and the protein sequence around the pinpointed amino acids from the NS3 and NS5 regions are also conserved. The identification of the functionally essential interaction between the two proteins by biochemical and reverse genetics methods paves the way for rational drug design efforts to inhibit viral RNA synthesis.
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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.