9XVJ

Crystal structure of Dengue 2 Virus NS2B/NS3 Protease

Summary for 9XVJ

• Entry DOI: 10.2210/pdb9xvj/pdb
• Descriptor: non-structural protein 2B, non-structural protein 3 protease, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: ns2b/ns3 protease, dengue virus, viral protein
• Biological source: dengue virus type 2; More
• Total number of polymer chains: 2
• Total formula weight: 25900.44

Authors

Zhu, H.J.,Niu, W.C.,Gong, Y.,Cao, P.,Zhou, Y.B. (deposition date: 2025-11-26, release date: 2026-10-28)

Primary citation

Zhu, H.,Niu, W.,Xu, Y.,Li, Z.,Xia, D.,Chen, S.,Zhang, B.,Wang, J.,Yang, H.,Gao, X.,Chen, Y.,Gong, Y.,Cao, P.,Zhou, Y.
Structural insights into DENV-2 NS2B-NS3 protease and inhibition by glutathione-coated gold nanocluster.
Arch Virol, 171:-, 2026

PubMed Abstract: Dengue virus (DENV) continues to pose a significant global health threat, with increasing infection rates and limited treatment options. The viral NS2B-NS3 protease (NS2B-NS3pro), a highly conserved two-component enzyme essential for polyprotein processing and replication, is a key target for antiviral drug development. Here, we report the 2.25 Å-resolution crystal structure of DENV serotype 2 (DENV-2) NS2B-NS3pro, in which a PEG fragment is bound within a solvent-exposed pocket between β10, β11, β14 and β15 of NS3. This structure reveals a previously unrecognized solvent-exposed PEG-binding pocket, which may represent a putative ligand-binding surface for future validation and inhibitor-design studies. We also show that the glutathione-coated gold nanocluster (GSH-AuNC) directly inhibits DENV-2 NS2B-NS3pro. Bio-layer interferometry and fluorescence-based protease assays indicate that the nanocluster binds NS2B-NS3pro with a dissociation constant of 15.64 µM and inhibits its catalytic activity with an IC of 16.04 µM, consistent with a direct inhibitory effect at the in vitro enzymatic level. Molecular dynamics simulations further suggest that GSH-AuNC is predicted to interact with the catalytic triad of NS2B-NS3pro, forming stable electrostatic and van der Waals interactions that may interfere with substrate access. Collectively, these findings provide an in vitro structural and biochemical basis for targeting DENV-2 NS2B-NS3pro and may inform future development of small-molecule or nanomedicine-based inhibitors, although cell-based antiviral efficacy, cytotoxicity, and cellular uptake remain to be evaluated.

PubMed: 42337180
DOI: 10.1007/s00705-026-06662-w

Experimental method

X-RAY DIFFRACTION (2.25 Å)