Abstract
Two potent inhibitors based on the crystal structure of influenza virus sialidase have been designed. These compounds are effective inhibitors not only of the enzyme, but also of the virus in cell culture and in animal models. The results provide an example of the power of rational, computer-assisted drug design, as well as indicating significant progress in the development of a new therapeutic or prophylactic treatment for influenza infection.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Langmuir, A. D., Worthen, T. D., Solomon, J., Ray, C. G. & Petersen, E. New Engl. J. Med. 313, 1027–1030 (1985).
Hay, A. J., Wolstenholme, A. J., Skehel, J. J. & Smith, M. H. EMBO J. 4, 3021–3024 (1985).
Pinto, L. H., Holsinger, L. J. & Lamb, R. A. Cell 69, 517–528 (1992).
Stoof, J. C., Booij, J., Drukarch, B. & Wolters, E. C. Eur. J. Pharmacol. 213, 439–443 (1992).
Hayden, F. G. et al. New Engl. J. Med. 321, 1696–1702 (1989).
Wilson, I. A., Skehel, J. J. & Wiley, D. C. Nature 289, 366–373 (1981).
Wiley, D. C., Wilson, I. A. & Skehel, J. J. Nature 289, 373–378 (1981).
Varghese, J. N., Laver, W. G. & Colman, P. M. Nature 303, 35–40 (1983).
Colman, P. M., Varghese, J. N. & Laver, W. G. Nature 303, 41–44 (1983).
Varghese, J. N. & Colman, P. M. J. molec. Biol. 221, 473–486 (1991).
Burmelster, W. P., Ruigrok, R. W. H. & Cusack, S. EMBO J. 11, 49–56 (1991).
Klenk, E., Faillard, H. & Lempfrid, H. Hoppe-Seyler's Z. physiol. Chem. 301, 235–246 (1955).
Gottschalk, A. Biochim. biophys. Acta 23, 645–646 (1957).
Drzeniek, R. Curr. Top. microbiol. Immun. 59, 35–74 (1972).
Schauer, R. Trends biochem. Sci. 10, 357–360 (1985).
Schauer, R. in Structural Carbohydrates in the Liver (eds Popper, H., Reutter, W., Köttgen, E. & Gudat, F.) 83–97 (MTP, Boston, 1983).
Chong, A. K. J., Pegg, M. S. & von Itzstein, M. Biochim. biophys. Acta 1077, 65–71 (1991).
Chong, A. K. J., Pegg, M. S. & von Itzstein, M. Biochem. Int. 24, 165–171 (1991).
Chong, A. K. J., Pegg, M. S., Taylor, N. R. & von Itzstein, M. Eur. J. Biochem. 207, 335–343 (1992).
Dimmock, N. J. J. gen. Virol. 13, 481–483 (1971).
Carroll, S. M. & Paulson, J. C. Arch. Virol. 71, 273–277 (1982).
Hirst, G. K. J. exp. Med. 76, 195–209 (1942).
Burnet, F. M. Aust. J. exp. Biol. med. Sci. 26, 381–387 (1948).
Gottschalk, A. Biochim. biophys. Acta 23, 645–646 (1957).
Palese, P., Jobita, K., Ueda, M. & Compans, R. W. Virology 61, 397–410 (1974).
Colman, P. M. & Ward, C. W. Curr. Top. microbiol. Immun. 114, 117–255 (1985).
Klenk, H.-D. & Rott, R. Adv. Virus Res. 34, 247–280 (1988).
Palese, P. & Schulman, J. L. in Chemoprophylaxis and Virus Infections of the Upper Respiratory Tract Vol. 1 (ed. Oxford, J. S.) 189–205 (CRC, Cleveland, 1977).
Varghese, J. N., McKimm-Breschkin, J., Caldwell, J. B., Kortt, A. A. & Colman, P. M. Proteins 14, 327–332 (1992).
Colman, P. M. in The Influenza Viruses (ed. Krug, R. M.) 175–218 (Plenum, New York, 1989).
Goodford, P. J. J. med. Chem. 28, 849–857 (1985).
Tintelnot, M. & Andrews, P. J. Comp.-Aided. molec. Design 3, 67–84 (1989).
von Itzstein, M., Jin, B., Wu, W.-Y. & Chandler, M. Carbohydr. Res. (in the press).
von Itzstein, M., Wu, W.-Y., Phan, T. V., Danylec, B. & Jin, B. Chem. Abs. 117, 49151y (1991).
Brunger, A. T. J. molec. Biol. 203, 803–816 (1988).
Potier, M., Mameli, L., Belisle, M., Dallaire, L. & Melancon, S. B. Analyt. Biochem. 94, 287–296 (1979).
Henderson, P. J. F. Biochem. J. 127, 321–333 (1972).
Meindl, P., Bodo, G., Palese, P., Schulman, J. L. & Tuppy, H. Virology 58, 457–463 (1974).
Holzer, C. T. et al. Glycoconjugate J. 10, 40–45 (1993).
Nöhle, U., Beau, J.-M. & Schauer, R. Eur. J. Biochem. 126, 543–548 (1982).
Leatherbarrow, R. J. Trends biochem. Sci. 15, 455–458 (1990).
Potier, M., Michaud, L., Tranchemontagne, J. & Thauvette, L. Biochem. J. 267, 197–202 (1990).
Hayden, F. G., Cote, K. M. & Douglas, R. G. Jr Antimicrob. Ag. Chemother. 17, 865–870 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
von Itzstein, M., Wu, WY., Kok, G. et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363, 418–423 (1993). https://doi.org/10.1038/363418a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/363418a0
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.