The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis
Open accessAbstract
More 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 (Kd) of ∼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.
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The origins and the future of microfluidics
Whitesides, G. M. (2006) · Nature · doi:10.1038/nature05058 · Cited by 9,687
How many drug targets are there?
Overington, J. P., Al-Lazikani, B., & Hopkins, A. L. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2199 · Cited by 3,505
Solvent Compatibility of Poly(dimethylsiloxane)-Based Microfluidic Devices
Lee, J. N., Park, C., & Whitesides, G. M. (2003) · Analytical Chemistry · doi:10.1021/ac0346712 · Cited by 2,643
Identification of HuR as a protein implicated in AUUUA‐mediated mRNA decay
Myer, V. E., Fan, X. C., & Steitz, J. A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.8.2130 · Cited by 302
Cited by
The HCV Life Cycle: In vitro Tissue Culture Systems and Therapeutic Targets
Gerold, G., & Pietschmann, T. (2014) · Digestive Diseases · doi:10.1159/000360830 · Cited by 4,854
Understanding the hepatitis C virus life cycle paves the way for highly effective therapies
Scheel, T. K. H., & Rice, C. M. (2013) · Nature Medicine · doi:10.1038/nm.3248 · Cited by 554
Current and Future Therapies for Hepatitis C Virus Infection
Liang, T. J., & Ghany, M. G. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1213651 · Cited by 490
Koh, C., Li, Q., & Liang, J. (2016) · Clinical Virology · doi:10.1128/9781555819439.ch54 · Cited by 321
Microfluidics for cell-based high throughput screening platforms—A review
Du, G., Fang, Q., & den Toonder, J. M. J. (2016) · Analytica Chimica Acta · doi:10.1016/j.aca.2015.11.023 · Cited by 276
Metadata
- Authors
- Einav, S., Gerber, D., Bryson, P. D., Sklan, E. H., Elazar, M., Maerkl, S. J., Glenn, J. S., & Quake, S. R.
- Venue
- Nature Biotechnology
- Published
- 2008-08-31
- Volume
- 26
- Issue
- 9
- Pages
- 1019-1027
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2113749416
- Cited by
- 235
- References
- 4
- FWCI
- 14.19
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Einav, S., Gerber, D., Bryson, P. D., Sklan, E. H., Elazar, M., Maerkl, S. J., Glenn, J. S., & Quake, S. R. (2008). Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis. Nature Biotechnology. https://doi.org/10.1038/nbt.1490
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