7IB3

Crystal structure of Zika NS2B-NS3 protease in complex with fragment EOS103134 from ECBL-96

This is a non-PDB format compatible entry.

Summary for 7IB3

• Entry DOI: 10.2210/pdb7ib3/pdb
• Group deposition: Zika NS2B-NS3 protease vs. ECBL-96 (G_1002347)
• Descriptor: NS2B co-factor, NS3 protease, 1-(1-ethyl-1H-pyrrol-3-yl)methanamine, ... (4 entities in total)
• Functional Keywords: crystallographic fragment screening, ns2b-ns3 zika protease, ecbl-96 fragment library, viral protein
• Biological source: Zika virus; More
• Total number of polymer chains: 4
• Total formula weight: 49609.74

Authors

Benz, L.S.,Wollenhaupt, J.,Jirgensons, A.,Miletic, T.,Mueller, U.,Weiss, M.S. (deposition date: 2025-05-21, release date: 2025-11-12)

Primary citation

Benz, L.S.,Wollenhaupt, J.,Jirgensons, A.,Miletic, T.,Mueller, U.,Weiss, M.S.
From fragments to follow-ups: rapid hit expansion by making use of EU-OPENSCREEN resources.
Rsc Med Chem, 2025

PubMed Abstract: Quite frequently, it is the progression of initial crystallographic fragment screening hits into more potent binders to their target, which constitutes the major bottleneck in many academic compound or drug development projects. While high quality starting points are critical to the success of a drug development project, it is equally important to have accessible pathways for further compound development. Here, we present two crystallographic fragment screening campaigns using a 96 fragment sub-selection of the European Fragment Screening Library (EFSL) provided by EU-OPENSCREEN. The two campaigns against the targets endothiapepsin and the NS2B-NS3 Zika protease, yielded hit rates of 31% and 18%, respectively. Further, we present how within the framework of the EU-OPENSCREEN European Research Infrastructure Consortium (ERIC) fast identification of follow-up compounds can be realized. With just one round of testing related compounds from the European Chemical Biology Library, two follow-up binders for each of the two targets could be identified proving the feasibility of this approach.

PubMed: 41132859
DOI: 10.1039/d5md00684h

Experimental method

X-RAY DIFFRACTION (1.61 Å)