5CZB

HCV NS5B IN COMPLEX WITH LIGAND IDX17119-5

Summary for 5CZB

• Entry DOI: 10.2210/pdb5czb/pdb
• Descriptor: NS5B, 1-[4-(7-amino-5-methylpyrazolo[1,5-a]pyrimidin-2-yl)phenyl]-3-{[(R)-(2,4-dimethylphenyl)(methoxy)phosphoryl]amino}-1H-pyrazole-4-carboxylic acid, GLYCEROL, ... (7 entities in total)
• Functional Keywords: hcv polymerase, idenix, inhibitor, proteros biostructures gmbh, replication
• Biological source: Hepatitis C virus subtype 1b (HCV)
• Cellular location: Core protein p21: Host endoplasmic reticulum membrane ; Single-pass membrane protein . Core protein p19: Virion . Envelope glycoprotein E1: Virion membrane ; Single-pass type I membrane protein . Envelope glycoprotein E2: Virion membrane ; Single-pass type I membrane protein . p7: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Protease NS2-3: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 5A: Host endoplasmic reticulum membrane ; Peripheral membrane protein . RNA-directed RNA polymerase: Host endoplasmic reticulum membrane ; Single-pass type I membrane protein : O92972
• Total number of polymer chains: 2
• Total formula weight: 129021.89

Authors

Pierra, C.,Dousson, C.,Augustin, M. (deposition date: 2015-07-31, release date: 2016-06-15, Last modification date: 2024-05-01)

Primary citation

Pierra Rouviere, C.,Amador, A.,Badaroux, E.,Convard, T.,Da Costa, D.,Dukhan, D.,Griffe, L.,Griffon, J.F.,LaColla, M.,Leroy, F.,Liuzzi, M.,Loi, A.G.,McCarville, J.,Mascia, V.,Milhau, J.,Onidi, L.,Paparin, J.L.,Rahali, R.,Sais, E.,Seifer, M.,Surleraux, D.,Standring, D.,Dousson, C.
Synthesis of potent and broad genotypically active NS5B HCV non-nucleoside inhibitors binding to the thumb domain allosteric site 2 of the viral polymerase.
Bioorg.Med.Chem.Lett., 26:4536-4541, 2016

PubMed Abstract: The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells and, as a consequence, is an attractive target for selective inhibition. This Letter describes the discovery of a new family of HCV NS5B non-nucleoside inhibitors, based on the bioisosterism between amide and phosphonamidate functions. As part of this program, SAR in this new series led to the identification of IDX17119, a potent non-nucleoside inhibitor, active on the genotypes 1b, 2a, 3a and 4a. The structure and binding domain of IDX17119 were confirmed by X-ray co-crystallization study.

PubMed: 27520942
DOI: 10.1016/j.bmcl.2016.01.042

Experimental method

X-RAY DIFFRACTION (1.96 Å)