3UDL

3-heterocyclyl quinolone bound to HCV NS5B

Summary for 3UDL

• Entry DOI: 10.2210/pdb3udl/pdb
• Descriptor: HCV NS5B polymerase, 3-(5-benzyl-1,2,4-oxadiazol-3-yl)-6-fluoro-1-[2-fluoro-4-(trifluoromethyl)benzyl]-7-(4-methylpiperazin-1-yl)quinolin-4(1H)-one (3 entities in total)
• Functional Keywords: hcv, polymerase, drug design, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Hepatitis C virus subtype 1b
• Total number of polymer chains: 4
• Total formula weight: 258796.11

Authors

Somoza, J.R. (deposition date: 2011-10-28, release date: 2011-12-21)

Primary citation

Kumar, D.V.,Rai, R.,Brameld, K.A.,Somoza, J.R.,Rajagopalan, R.,Janc, J.W.,Xia, Y.M.,Ton, T.L.,Shaghafi, M.B.,Hu, H.,Lehoux, I.,To, N.,Young, W.B.,Green, M.J.
Quinolones as HCV NS5B polymerase inhibitors.
Bioorg.Med.Chem.Lett., 21:82-87, 2011

PubMed Abstract: Hepatitis C virus (HCV) infection is treated with a combination of peginterferon alfa-2a/b and ribavirin. To address the limitations of this therapy, numerous small molecule agents are in development, which act by directly affecting key steps in the viral life-cycle. Herein we describe our discovery of quinolone derivatives, novel small-molecules that inhibit NS5b polymerase, a key enzyme of the viral life-cycle. A crystal structure of a quinoline analog bound to NS5B reveals that this class of compounds binds to allosteric site-II (non-nucleoside inhibitor-site 2, NNI-2) of this protein.

PubMed: 21145235
DOI: 10.1016/j.bmcl.2010.11.068

Experimental method

X-RAY DIFFRACTION (2.174 Å)