Evidence map›Paper›PMID 41833763›Full record

ArticleJournal of structural biology2026

An inactive Zika NS2B-NS3pro protease construct for investigating allosteric inhibitors.

Khac Huy Ngo, Simon Lattmann, Paulina Duhita Anindita, Chong Wai Liew, Reuben S Harris, Dahai Luo, CongBao Kang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of structural biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

7 authors.

Khac Huy NgoLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Simon LattmannNTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore.
Paulina Duhita AninditaLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
Chong Wai LiewExperimental Drug Development Centre, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Reuben S HarrisDepartment of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, Texas, United States; Howard Hughes Medical Institute, University of Texas Health San Antonio, San Antonio, Texas, United States.
Dahai LuoLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore. Electronic address: LuoDahai@ntu.edu.sg.
CongBao KangExperimental Drug Development Centre, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. Electronic address: kang_congbao@eddc.sg.

Funding

Project 5: Pandemic Virus Helicase InhibitorsU19AI171954 · NIAID · UNIVERSITY OF MINNESOTA · PI Reuben S Harris, Fang Li · 2022 to 2026
$100.9M
NIAID NIH HHS U19 AI171954
6 · The paper itself

Abstract

The Zika virus protease, composed of the cofactor region from NS2B and the N-terminal region of NS3, plays a critical role in viral polyprotein maturation and represents an attractive therapeutic target. However, developing small-molecule inhibitors for its highly hydrophilic active site remains challenging, highlighting the importance of pursuing allosteric inhibition strategies. In this study, we engineered an NS2B-NS3 protease containing an 18-residue NS2B sequence linked to the N-terminal region of NS3 via a glycine-rich linker. We determined its crystal structure and obtained the solution NMR spectrum with backbone resonance assigned. This new construct was used in fragment screening and two new fragments were identified. This design excludes the C-terminal part of NS2B cofactor region, whose conformation is influenced by substrate or inhibitor binding, making the construct particularly valuable for screening and characterizing allosteric inhibitors.

Indexed as

Protease InhibitorsRNA HelicasesSerine EndopeptidasesViral Nonstructural ProteinsZika VirusAllosteric RegulationCatalytic DomainCrystallography, X-RayDEAD-box RNA HelicasesModels, MolecularNucleoside-TriphosphataseProtein ConformationViral ProteasesDEAD-box RNA HelicasesNS2B protein, flavivirusNS3 protein, Zika virusNucleoside-TriphosphataseProtease InhibitorsRNA HelicasesSerine EndopeptidasesViral Nonstructural ProteinsViral ProteasesAllosteric inhibitorsFragment screeningNMR spectroscopyX-ray crystallographyZika virus

Identifiers

PMID41833763
PMCPMC13571211

What OpenQuestion holds

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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.