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PDBsum entry 4cdq
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Contents |
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297 a.a.
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245 a.a.
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242 a.a.
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58 a.a.
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References listed in PDB file
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Key reference
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Title
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More-Powerful virus inhibitors from structure-Based analysis of hev71 capsid-Binding molecules.
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Authors
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L.De colibus,
X.Wang,
J.A.Spyrou,
J.Kelly,
J.Ren,
J.Grimes,
G.Puerstinger,
N.Stonehouse,
T.S.Walter,
Z.Hu,
J.Wang,
X.Li,
W.Peng,
D.J.Rowlands,
E.E.Fry,
Z.Rao,
D.I.Stuart.
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Ref.
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Nat Struct Biol, 2014,
21,
282-288.
[DOI no: ]
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PubMed id
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Abstract
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Enterovirus 71 (HEV71) epidemics in children and infants result mainly in mild
symptoms; however, especially in the Asia-Pacific region, infection can be
fatal. At present, no therapies are available. We have used structural analysis
of the complete virus to guide the design of HEV71 inhibitors. Analysis of
complexes with four 3-(4-pyridyl)-2-imidazolidinone derivatives with varying
anti-HEV71 activities pinpointed key structure-activity correlates. We then
identified additional potentially beneficial substitutions, developed methods to
reliably triage compounds by quantum mechanics-enhanced ligand docking and
synthesized two candidates. Structural analysis and in vitro assays confirmed
the predicted binding modes and their ability to block viral infection. One
ligand (with IC50 of 25 pM) is an order of magnitude more potent than the best
previously reported inhibitor and is also more soluble. Our approach may be
useful in the design of effective drugs for enterovirus infections.
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Secondary reference #1
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Title
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A sensor-Adaptor mechanism for enterovirus uncoating from structures of ev71.
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Authors
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X.Wang,
W.Peng,
J.Ren,
Z.Hu,
J.Xu,
Z.Lou,
X.Li,
W.Yin,
X.Shen,
C.Porta,
T.S.Walter,
G.Evans,
D.Axford,
R.Owen,
D.J.Rowlands,
J.Wang,
D.I.Stuart,
E.E.Fry,
Z.Rao.
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Ref.
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Nat Struct Biol, 2012,
19,
424-429.
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PubMed id
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