2O5D

Thiazolone-acylsulfonamides as novel HCV NS5B polymerase allosteric inhibitors: Convergence of structure-based drug design and X-ray crystallographic study

Summary for 2O5D

• Entry DOI: 10.2210/pdb2o5d/pdb
• Descriptor: HCV, (2S)-2-({(5Z)-5-[(5-ETHYL-2-FURYL)METHYLENE]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-2-YL}AMINO)-2-(4-FLUOROPHENYL)-N-[(4-NITROPHENYL)SULFONYL]ACETAMIDE (3 entities in total)
• Functional Keywords: hcv, ns5b, viral rna-directed rna polymerase, rdrp, allosteric inhibitor, hcv inhibitor complex, structure-based drug design, viral protein
• Biological source: Hepatitis C virus
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein. Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P26663
• Total number of polymer chains: 2
• Total formula weight: 129143.77

Authors

Yao, N. (deposition date: 2006-12-05, release date: 2007-02-20, Last modification date: 2023-12-27)

Primary citation

Yan, S.,Appleby, T.,Larson, G.,Wu, J.Z.,Hamatake, R.K.,Hong, Z.,Yao, N.
Thiazolone-acylsulfonamides as novel HCV NS5B polymerase allosteric inhibitors: Convergence of structure-based drug design and X-ray crystallographic study.
Bioorg.Med.Chem.Lett., 17:1991-1995, 2007

PubMed Abstract: A novel series of thiazolone-acylsulfonamides were designed as HCV NS5B polymerase allosteric inhibitors. The structure based drug designs (SBDD) were guided by docking results that revealed the potential to explore an additional pocket in the allosteric site. In particular, the designed molecules contain moieties of previously described thiazolone and a newly designed acylsulfonamide linker that is in turn connected with a substituted aromatic ring. The selected compounds were synthesized and demonstrated low muM activity. The X-ray complex structure was determined at a 2.2A resolution and converged with the SBDD principle.

PubMed: 17276060
DOI: 10.1016/j.bmcl.2007.01.024

Experimental method

X-RAY DIFFRACTION (2.2 Å)