• 1
    Cuthbert, J.A. (1994) Hepatitis C: progress and problem. Clin. Microbiol. Rev. 7, 505 532.
  • 2
    Di Bisceglie, A.M. (1995) Hepatitis C and hepatocellular carcinoma. Semin. Liver. Dis. 15, 64 69.
  • 3
    Kato, N., Hijikata, M., Ootsuyama, Y., Nakagawa, M., Ohkoshi, S., Sugimura, T., Shimotohno, K. (1990) Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc. Natl Acad. Sci. USA 87, 9524 9528.
  • 4
    Choo, Q.-L., Richman, K., Han, J.H., Berger, K., Lee, C., Dong, C., Gallegos, C., Coit, D., Medina-Selby, A., Barr, P., Weiner, A.J., Bradley, D.W., Kuo, G., Houghton, M. (1991) Genetic organization and diversity of the hepatitis C virus. Proc. Natl Acad. Sci. USA 88, 2451 2455.
  • 5
    Takamizawa, A., Mori, C., Fuke. I., Manabe, S., Murakami, S., Fujita, J., Onishi, E., Andoh, T., Yoshida, I., Okayama, H. (1991) Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol. 65, 1105 1113.
  • 6
    Mizushima, H., Hijikata, M., Tanji, Y., Kimura, K., Shimotohno, K. (1994) Analysis of N-terminal processing of hepatitis C virus nonstructural protein 2. J. Virol. 68, 2731 2734.
  • 7
    Hijikata, M., Kato, N., Ootsuyama, Y., Nakagawa, M., Shimotohno, K. (1991) Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc. Natl Acad. Sci. USA 88, 5547 5551.
  • 8
    Lin, C., Lindenbach, B.D., Pragai, B., McCourt, D.W., Rice, C.M. (1994) Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. J. Virol. 68, 5063 5073.
  • 9
    Hijikata, M., Mizushima, T., Akagi, S., Mori, S., Kakiuchi, N., Kato, N., Tanaka, T., Kimura, K., Shimotohno, K. (1993) Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus. J. Virol. 67, 4665 4675.
  • 10
    Grakoui, A., McCourt, D.W., Wychowski, C., Feinstone, S.M., Rice, C.M. (1993) A second hepatitis C virus-encoded proteinase. Proc. Natl Acad. Sci. USA 90, 10583 10587.
  • 11
    Grakoui, A., McCourt, D.W., Wychowski, C., Feinstone, S.M., Rice, C.M. (1993) Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites. J. Virol. 67, 2832 2843.
  • 12
    Tomei, L., Failla, C., Santolini, E., DeFrancesco, R., LaMonica, N. (1993) NS3 is a serine protease required for processing of hepatitis C virus polyprotein. J. Virol. 67, 4017 4026.
  • 13
    Manabe, S., Fuke, I., Tanishita, O., Kaji, C., Gomi, Y., Yoshida, S., Mori, C., Takamizawa, A., Yashida, I., Okayama, H. (1994) Production of nonstructural proteins of hepatitis C virus requires a putative viral protease encoded by NS3. Virology 198, 636 644.DOI: 10.1006/viro.1994.1075
  • 14
    Bartenschlager, R., Ahlborn-Laake, L., Mous, J., Jacobsen, H. (1993) Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions. J. Virol. 67, 3835 3844.
  • 15
    Kim, D.W., Gwack, Y., Han, J.H., Choe, J. (1995) C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase activity. Biochem. Biophys. Res. Commun. 215, 160 166.DOI: 10.1006/bbrc.1995.2447
  • 16
    Failla, C., Tomei, L., De Francesco, R. (1994) Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J. Virol. 68, 3753 3760.
  • 17
    Lin, C. & Rice, C.M. (1995) The hepatitis C virus NS3 serine proteinase and NS4A cofactor: establishment of a cell-free trans-processing assay. Proc. Natl Acad. Sci. USA 92, 7622 7626.
  • 18
    Shimizu, Y., Yamaji, K., Masuho, Y., Yokota, T., Inoue, H., Sudo. K., Satoh, S., Shimotohno, K. (1996) Identification of the sequence on NS4A required for enhanced cleavage of the NS5A/5B site by hepatitis C virus NS3 protease. J. Virol. 70, 127 132.
  • 19
    Tanji, Y., Hijikata, M., Satoh, S., Kaneko, T., Shimotohno, K. (1995) Hepatitis C virus-encoded nonstructural protein NS4A has versatile functions in viral protein processing. J. Virol. 69, 1575 1581.
  • 20
    Love, R.A., Parge, H.E., Wickersham, J.A., Hostomsky, Z., Habuka, N., Moomaw, E.W., Adachi, T., Hostomska, Z. (1996) The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 87, 331 342.
  • 21
    Kim, J.L., Morgenstern, K.A., Lin, C., Fox, T., Dwyer, M.D., Landro, J.A., Chambers, S.P., Markland, W., Lepre, C.A., O'Malley, E.T., Harbeson, S.L., Rice, C.M., Murcko, M.A., Caron, P.R., Thomson, J.A. (1996) Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 87, 343 355.
  • 22
    Yao, N., Hesson, T., Cable, M., Hong, Z., Kwong, A.D., Le, H.V., Weber, P.C. (1997) Structure of the hepatitis C virus RNA helicase domain. Nat. Struct. Biol. 4, 463 467.
  • 23
    Kim, J.L., Morgenstern, K.A., Griffith, J.P., Dwyer, M.D., Thomson, J.A., Murcko, M.A., Lin, C., Caron, P.R. (1998) Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding. Structure 6, 89 100.
  • 24
    Urvil, P.T., Kakiuchi, N., Zhou, D.-M., Shimotohno, K., Kumar, P.K.R., Nishikawa, S. (1997) Selection of RNA aptamers that bind specifically to the NS3 protease of hepatitis C virus. Eur. J. Biochem. 248, 130 138.
  • 25
    Kumar, P.K., Machida, K., Urvil, P.T., Kakiuchi, N., Vishnuvardhan, D., Shimotohno, K., Taira, K., Nishikawa, S. (1997) Isolation of RNA aptamers specific to the NS3 protein of hepatitis C virus from a pool of completely random RNA. Virology 237, 270 282.DOI: 10.1006/viro.1997.8773
  • 26
    Joyce, G.F. (1989) Amplification, mutation and selection of catalytic RNA. Gene 82, 83 87.
  • 27
    Tuerk, C. & Gold, L. (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505 510.
  • 28
    Ellington, A.D. & Szostak, J.W. (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818 822.
  • 29
    Jayasena, S.D. (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin. Chem. 45, 1628 1650.
  • 30
    Vishnuvardhan, D., Kakiuchi, N., Urvil, P.T., Shimotohno, K., Kumar, P.K.R., Nishikawa, S. (1997) Expression of highly active recombinant NS3 protease domain of hepatitis C virus in E. coli. FEBS Lett. 402, 209 212.DOI: 10.1016/s0014-5793(96)01532-3
  • 31
    Kakiuchi, N., Hijikata, M., Komoda, Y., Tanji, Y., Hirowatari, Y., Shimotohno, K. (1995) Bacterial expression and analysis of cleavage activity of HCV serine proteinase using recombinant and synthetic substrate. Biochem. Biophys. Res. Commun. 210, 1059 1065.DOI: 10.1006/bbrc.1995.1764
  • 32
    Zuker, M. (1989) Computer prediction of RNA structure. Methods Enzymol. 180, 202 287.
  • 33
    Gal, S.W., Amontov, S., Urvil, P.T., Vishnuvardhan, D., Nishikawa, F., Kumar, P.K., Nishikawa, S. (1998) Selection of a RNA aptamer that binds to human activated protein C and inhibits its protease function. Eur. J. Biochem. 252, 553 562.
  • 34
    Ingallinella, P., Altamura, S., Bianchi, E., Taliani, M., Ingenito, R., Cortese, R., De Francesco, R., Steinkuhler, C., Pessi, A. (1998) Potent peptide inhibitors of human hepatitis C virus NS3 protease are obtained by optimizing the cleavage products. Biochemistry 37, 8906 8914.
  • 35
    Martin, F., Dimasi, N., Volpari, C., Perrera, C., Di Marco, S., Brunetti, M., De Francesco, R., Sollazzo, M. (1998) Design of selective eglin inhibitors of HCV NS3 proteinase. Biochemistry 37, 11459 11468.
  • 36
    Sudo, K., Matsumoto, Y., Matsushima, M., Fujiwara, M., Konno, K., Shimotohno, K., Shigeta, S., Yokota, T. (1997) Novel hepatitis C virus protease inhibitors: thiazolidine derivatives. Biochem. Biophys. Res. Comm. 238, 643 647.
  • 37
    Martin, F., Volpari, C., Steinkuhler, C., Dimasi, N., Brunetti, M., Biasiol, G., Altamura, S., Cortese, R., De Francesco, R., Sollazzo, M. (1997) Affinity selection of a camelized V (H) domain antibody inhibitor of hepatitis C virus NS3 protease. Protein Eng. 10, 607 614.
  • 38
    Kakiuchi, N., Komoda, Y., Komoda, K., Takeshita, N., Okada, S., Tani, T., Shimotohno, K. (1998) Non-peptide inhibitors of HCV serine proteinase. FEBS Lett. 421, 217 220.DOI: 10.1016/s0014-5793(97)01566-4
  • 39
    Padmanabhan, K., Padmanabhan, K.P., Ferrara, J.D., Sadler, J.E., Tulinsky, A. (1993) The structure of α-thrombin inhibited by a 15-mer single-stranded DNA aptamer. J. Biol. Chem. 268, 17651 17654.
  • 40
    Paborsky, L.R., McCurdy, S.N., Griffin, L.C., Toole, J.J., Leung, L.L. (1993) The single-stranded DNA aptamer-binding site of human thrombin. J. Biol. Chem. 268, 20808 20811.