ArticleJournal of virology2004
Identification of residues in the dengue virus type 2 NS2B cofactor that are critical for NS3 protease activation.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Animal venoms as a source of antiviral peptides active against arboviruses: a systematic review.Archives of virology · 2022Pooled it
- Achievements and Approaches in the Search for Small-Molecule Dengue NS2B/NS3 Inhibitors.Current medicinal chemistry · 2026Review
- An investigation of fucoidan as a potential inhibitor against DENV/NS3 proteases through molecular dynamics simulations and DFT studies.Journal of molecular modeling · 2025Article
- Identification of Potential Inhibitors Targeting Non-Structural Proteins NS3 and NS5 of Dengue Virus Using Docking and Deep Learning Approaches.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Evolution and adaptation of dengue virus in response to high-temperature passaging in mosquito cells.Virus evolution · 2025Article
- NS2B-D55E and NS2B-E65D Variations Are Responsible for Differences in NS2B-NS3 Protease Activities Between Japanese Encephalitis Virus Genotype I and III in Fluorogenic Peptide Model.International journal of molecular sciences · 2024Article
- Pan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formation.Nature communications · 2024Article
- Dengue Virus 2 NS2B Targets MAVS and IKKε to Evade the Antiviral Innate Immune Response.Journal of microbiology and biotechnology · 2023Article
- Flavivirus proteases: The viral Achilles heel to prevent future pandemics.Antiviral research · 2023Review
- A fast-growing dengue virus mutant reveals a dual role of STING in response to infection.Open biology · 2022Article
- Identification and In Silico Binding Study of a Highly Potent DENV NS2B-NS3 Covalent Inhibitor.ACS medicinal chemistry letters · 2022Article
- Article
- Antiviral Agents against Flavivirus Protease: Prospect and Future Direction.Pathogens (Basel, Switzerland) · 2022Review
- Review
- The Future ofMolecules (Basel, Switzerland) · 2021Review
- Article
- Application of niclosamide and analogs as small molecule inhibitors of Zika virus and SARS-CoV-2 infection.Bioorganic & medicinal chemistry letters · 2021Article
- Identification of Cleavage Sites Proteolytically Processed by NS2B-NS3 Protease in Polyprotein of Japanese Encephalitis Virus.Pathogens (Basel, Switzerland) · 2021Article
- Methylene blue is a potent and broad-spectrum inhibitor against Zika virusEmerging microbes & infections · 2020Article
- Determinants of duck Tembusu virus NS2A/2B polyprotein procession attenuated viral replication and proliferation in vitro.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolytic processing of the dengue virus polyprotein is mediated by host cell proteases and the virus-encoded NS2B-NS3 two-component protease. The NS3 protease represents an attractive target for the development of antiviral inhibitors. The three-dimensional structure of the NS3 protease domain has been determined, but the structural determinants necessary for activation of the enzyme by the NS2B cofactor have been characterized only to a limited extent. To test a possible functional role of the recently proposed Phix(3)Phi motif in NS3 protease activation, we targeted six residues within the NS2B cofactor by site-specific mutagenesis. Residues Trp62, Ser71, Leu75, Ile77, Thr78, and Ile79 in NS2B were replaced with alanine, and in addition, an L75A/I79A double mutant was generated. The effects of these mutations on the activity of the NS2B(H)-NS3pro protease were analyzed in vitro by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of autoproteolytic cleavage at the NS2B/NS3 site and by assay of the enzyme with the fluorogenic peptide substrate GRR-AMC. Compared to the wild type, the L75A, I77A, and I79A mutants demonstrated inefficient autoproteolysis, whereas in the W62A and the L75A/I79A mutants self-cleavage appeared to be almost completely abolished. With exception of the S71A mutant, which had a k(cat)/K(m) value for the GRR-AMC peptide similar to that of the wild type, all other mutants exhibited drastically reduced k(cat) values. These results indicate a pivotal function of conserved residues Trp62, Leu75, and Ile79 in the NS2B cofactor in the structural activation of the dengue virus NS3 serine protease.
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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.