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The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine
Abstract
Hepatitis C virus (HCV) cannot be grown in vitro, making biochemical identification of new drug targets especially important. HCV p7 is a small hydrophobic protein of unknown function, yet necessary for particle infectivity in related viruses [Harada, T. et al., (2000) J. Virol. 74, 9498–9506]. We show that p7 can be cross‐linked in vivo as hexamers. Escherichia coli expressed p7 fusion proteins also form hexamers in vitro. These and HIS‐tagged p7 function as calcium ion channels in black lipid membranes. This activity is abrogated by Amantadine, a compound that inhibits ion channels of influenza [Hay, A.J. et al. (1985) EMBO J. 4, 3021–3024; Duff, K.C. and Ashley, R.H. (1992) Virology 190, 485–489] and has recently been shown to be active in combination with current HCV therapies.
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Cited by
Koutsoudakis, G., Kaul, A., Steinmann, E., Kallis, S., Lohmann, V., Pietschmann, T., & Bartenschlager, R. (2006) · Journal of Virology · doi:10.1128/jvi.02460-05 · Cited by 414
Pavlović, D., Neville, D. C. A., Argaud, O., Blumberg, B., Dwek, R. A., Fischer, W. B., & Zitzmann, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031527100 · Cited by 390
Gonzalez, M. E., & Carrasco, L. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00780-4 · Cited by 359
Metadata
- Authors
- Griffin, S. D. C., Beales, L. P., Clarke, D. S., Worsfold, O., Evans, S. D., Jaeger, J., Harris, M. P. G., & Rowlands, D. J.
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2002-12-21
- Volume
- 535
- Issue
- 1-3
- Pages
- 34-38
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2050997685
- Cited by
- 497
- References
- 0
- FWCI
- 14.30
- Type
- journal article
- Language
- en
- Open access
- closed
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- Griffin, S. D. C., Beales, L. P., Clarke, D. S., Worsfold, O., Evans, S. D., Jaeger, J., Harris, M. P. G., & Rowlands, D. J. (2003). The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. FEBS Letters. https://doi.org/10.1016/s0014-5793(02)03851-6
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