Evidence map›Paper›PMID 22031935›Full record

ArticleJournal of virology2012

Ligand-bound structures of the dengue virus protease reveal the active conformation.

Christian G Noble, Cheah Chen Seh, Alexander T Chao, Pei Yong Shi

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 2 pooled it
13.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 294 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  9. Review
  10. Zika NS2B Protein: In Vitro Formation of Large Multimeric Networks.International journal of molecular sciences · 2026
    Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Paritaprevir as a pan-antiviral against different flaviviruses.Frontiers in molecular biosciences · 2025
    Article

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Christian G NobleNovartis Institute for Tropical Diseases, Chromos, Singapore. christian.noble@novartis.com
Cheah Chen Seh
Alexander T Chao
Pei Yong Shi
Novartis (Singapore) · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dengue is a mosquito-borne viral hemorrhagic disease that is a major threat to human health in tropical and subtropical regions. Here we report crystal structures of a peptide covalently bound to dengue virus serotype 3 (DENV-3) protease as well as the serine-protease inhibitor aprotinin bound to the same enzyme. These structures reveal, for the first time, a catalytically active, closed conformation of the DENV protease. In the presence of the peptide, the DENV-3 protease forms the closed conformation in which the hydrophilic β-hairpin region of NS2B wraps around the NS3 protease core, in a manner analogous to the structure of West Nile virus (WNV) protease. Our results confirm that flavivirus proteases form the closed conformation during proteolysis, as previously proposed for WNV. The current DENV-3 protease structures reveal the detailed interactions at the P4' to P3 sites of the substrate. The new structural information explains the sequence preference, particularly for long basic residues in the nonprime side, as well as the difference in substrate specificity between the WNV and DENV proteases at the prime side. Structural analysis of the DENV-3 protease-peptide complex revealed a pocket that is formed by residues from NS2B and NS3; this pocket also exists in the WNV NS2B/NS3 protease structure and could be targeted for potential antivirus development. The structural information presented in the current study is invaluable for the design of specific inhibitors of DENV protease.

Indexed as

Amino Acid SequenceCatalytic DomainCrystallizationDengue VirusHumansLigandsModels, MolecularMolecular Sequence DataPeptide HydrolasesProtein BindingProtein ConformationSerine EndopeptidasesViral Nonstructural ProteinsViral ProteasesLigandsNS3 protease, dengue virusPeptide HydrolasesSerine EndopeptidasesViral Nonstructural ProteinsViral Proteases

Identifiers

PMID22031935
PMCPMC3255909
OpenAlexW2133545486

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.