000126229 001__ 126229
000126229 005__ 20190316234328.0
000126229 037__ $$aARTICLE
000126229 245__ $$aDiscovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis
000126229 269__ $$a2008
000126229 260__ $$c2008
000126229 336__ $$aJournal Articles
000126229 520__ $$aMore effective therapies are urgently needed against hepatitis C virus (HCV), a major cause of viral hepatitis. We used in vitro protein expression and microfluidic affinity analysis to study RNA binding by the HCV transmembrane protein NS4B, which plays an essential role in HCV RNA replication. We show that HCV NS4B binds RNA and that this binding is specific for the 3' terminus of the negative strand of the viral genome with a dissociation constant (K(d)) of approximately 3.4 nM. A high-throughput microfluidic screen of a compound library identified 18 compounds that substantially inhibited binding of RNA by NS4B. One of these compounds, clemizole hydrochloride, was found to inhibit HCV RNA replication in cell culture that was mediated by its suppression of NS4B's RNA binding, with little toxicity for the host cell. These results yield new insight into the HCV life cycle and provide a candidate compound for pharmaceutical development.
000126229 6531_ $$amicrofluidics
000126229 6531_ $$adrug discovery
000126229 6531_ $$aMITOMI
000126229 6531_ $$ahepatitis C
000126229 700__ $$aEinav, S.
000126229 700__ $$aGerber, D.
000126229 700__ $$aBryson, PD
000126229 700__ $$aSklan, EH
000126229 700__ $$aElazar, M.
000126229 700__ $$0243949$$aMaerkl, SJ$$g182445
000126229 700__ $$aGlenn, JS
000126229 700__ $$aQuake, SR
000126229 773__ $$tNature Biotechnology
000126229 8564_ $$s486973$$uhttps://infoscience.epfl.ch/record/126229/files/Einav_2008.pdf$$yn/a$$zn/a
000126229 909C0 $$0252240$$pLBNC$$xU11835
000126229 909CO $$ooai:infoscience.tind.io:126229$$pSTI$$particle$$qGLOBAL_SET
000126229 917Z8 $$x182445
000126229 937__ $$aLBNC-ARTICLE-2008-003
000126229 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000126229 980__ $$aARTICLE