9QRJ

Protein Kinase CK2 and bivalent inhibitors

This is a non-PDB format compatible entry.

Summary for 9QRJ

• Entry DOI: 10.2210/pdb9qrj/pdb
• Descriptor: Casein kinase II subunit alpha, SULFATE ION, 5-[6-[(3-chloranyl-4-phenyl-phenyl)methylamino]hexylamino]benzo[c][2,6]naphthyridine-8-carboxylic acid, ... (4 entities in total)
• Functional Keywords: protein kinase inhibitor bivalent ad pocket, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 87349.84

Authors

Krimm, I.,Gelin, M.,Guichou, J.F.,Grenier, D. (deposition date: 2025-04-03, release date: 2025-07-30)

Primary citation

Grenier, D.,Lopez Molina, D.S.,Gelin, M.,Mularoni, A.,Guichou, J.F.,Delcros, J.G.,Martinasso, C.,Yang, Y.,Ahnou, N.,Pawlotsky, J.M.,Ahmed-Belkacem, A.,Krimm, I.
Picomolar bivalent inhibitors of protein kinase CK2 active against beta-coronavirus replication.
Eur.J.Med.Chem., 296:117826-117826, 2025

PubMed Abstract: The protein casein kinase 2 (CK2) has been shown to be upregulated in SARS-CoV-2 infections. However, few inhibitors have been tested for antiviral activity against coronaviruses. In this study, highly potent and selective bivalent inhibitors targeting the protein kinase CK2 were developed. The chemical structure of the well-known inhibitor CX-4945 was used as an anchor for the ATP-binding site and was linked by polar and aliphatic linkers to chemical structures that bind the cryptic αD pocket of CK2. The bivalent inhibitor Biv5, which demonstrated a sub-nanomolar kinase inhibition, showed potent antiviral activity against SARS-CoV-2 in HEK-ACE2-TMPRSS2 and Vero cells. In addition, Biv5 significantly reduced viral replication over time in an ex vivo model of primary human nasal epithelial cells. The selectivity of Biv5 was tested against 16 kinases targeted by CX-4945, confirming that targeting the αD pocket confers high selectivity for CK2 to such inhibitors.

PubMed: 40482595
DOI: 10.1016/j.ejmech.2025.117826

Experimental method

X-RAY DIFFRACTION (2.73 Å)