Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection

Antimicrobial Agents and Chemotherapy

Volumn 42, Issue 3, 1998, Pages 640-646

  Mendel, Dirk B ^a   Tai, Chun Y ^a   Escarpe, Paul A ^a   Li, Weixing ^a   Sidwell, Robert W ^b   Huffman, John H ^b   Sweet, Clive ^c   Jakeman, Kenneth J ^c   Merson, James ^d   Lacy, Steven A ^a   Lew, Willard ^a   Williams, Matthew A ^a   Zhang, Lijun ^a   Chen, Ming S ^a   Bischofberger, Norbert ^a   Kim, Choung U ^a  

^a GILEAD SCIENCES   (United States)

^b UTAH STATE UNIVERSITY   (United States)

^c UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^d PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 ACETAMIDO 5 AMINO 3 (1 ETHYLPROPOXY) 1 CYCLOHEXENE 1 CARBOXYLIC ACID; OSELTAMIVIR; PRODRUG; SIALIDASE INHIBITOR; UNCLASSIFIED DRUG; VIRUS SIALIDASE; ZANAMIVIR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; FEMALE; FERRET; FEVER; INFLUENZA; INFLUENZA VIRUS A; INFLUENZA VIRUS B; MOUSE; NONHUMAN; NOSE BREATHING; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; SNEEZING; SURVIVAL RATE; VIRUS REPLICATION;

EID: 0031919227     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/aac.42.3.640     Document Type: Article

References (47)

1. Burmeister, W. P., R. W. Ruigrok, and S. Cusack. 1992. The 2.2 Å resolution crystal structure of influenza B neuraminidase and its complex with sialic acid. EMBO J. 11:49-56.
2. Burnet, F. M. 1948. Mucins and mucoids in relation to influenza virus action. Aust. J. Exp. Biol. Med. Sci. 26:381-387.
3. Chong, A. K., M. S. Pegg, and M. von Itzstein. 1991. Characterisation of an ionisable group involved in binding and catalysis by sialidase from influenza virus. Biochem. Int. 24:165-171.
4. Chong, A. K. J., M. S. Pegg, N. R. Taylor, and M. von Itzstein. 1992. Evidence for a sialosyl cation transition-state complex in the reaction of sialidase from influenza virus. Eur. J. Biochem. 207:335-343.
5. Colman, P. M. 1989. Neuraminidase: enzyme and antigen, p. 175-218. In R. M. Krug (ed.), The influenza viruses. Plenum, New York, N.Y.
6. Colman, P. M., P. A. Hoyne, and M. C. Lawrence. 1993. Sequence and structure alignment of paramyxovirus hemagglutinin-neuraminidase with influenza virus neuraminidase. J. Virol. 67:2972-2980.
7. Couch, R. B., W. Keitel, T. R. Cate, J. A. Quarles, L. A. Taber, and W. P. Glezen. 1996. Prevention of influenza virus infections by current inactivated influenza virus vaccines, p. 97-106. In L. E. Brown, A. W. Hampson, and R. G. Webster (ed.), Options for the control of influenza III. Elsevier, Amsterdam, The Netherlands.
8. Dixon, M. 1953. The determination of enzyme inhibitor constants. Biochem. J. 55:170-171.
9. Eisenberg, E. J., A. Bidgood, and K. C. Cundy. 1997. Penetration of GS4071, a novel influenza neuraminidase inhibitor, into rat bronchoalveolar lining fluid following oral administration of the prodrug GS4104. Antimicrob. Agents Chemother. 41:1949-1952.
10. Greffard, A., J. C. Pairon, H. Terzidis-Trabelsh, J.-M. Heslan, J. Bignon, C. R. Lambre, and Y. Pilatte. 1994. Initial characterization of human thymocyte sialidase activity: evidence that this enzymatic system is not altered during the course of T-cell maturation. Int. J. Biochem. 26:769-776.
11. Hayden, F., K. Cote, and R. G. Douglas, Jr. 1980. Plaque inhibition assay for drug susceptibility testing of influenza viruses. Antimicrob. Agents Chemother. 17:865-870.
12. Hayden, F. G., and H. J. Hay. 1992. Emergence and transmission of influenza A viruses resistant to amantadine and rimantidine. Curr. Top. Microbiol. Immunol. 176:119-130.
13. Hayden, F. G., M. Lobo, J. J. Treanor, M. Miller, and R. G. Mills. 1997. Efficacy and tolerability of oral GS 4104 for early treatment of experimental influenza in humans, abstr LB-26, p. 7. In 37th Interscience Conference on Antimicrobial Agents and Chemotherapy Program Addendum. American Society for Microbiology, Washington, D.C.
14. Hayden, F. G., A. D. M. E. Osterhaus, J. J. Treanor, D. M. Fleming, F. Y. Aoki, K. G. Nicholson, A. M. Bohnen, H. M. Hirst, O. Keene, and K. Wightman. 1997. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. N. Engl. J. Med. 337: 874-880.
15. Hayden, F. G., B. S. Rollins, and L. K. Madren. 1994. Anti-influenza virus activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en in cell culture and in human respiratory epithelium. Antivir. Res. 25:123-131.
16. Hayden, F. G., J. J. Treanor, A. F. Betts, M. Lobo, J. D. Esinhart, and E. K. Hussey. 1996. Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza. JAMA 275:295-299.
17. Huffman, J. H., R. W. Sidwell, D. L. Barnard, A. Morrison, M. J. Otto, C. L. Hill, and R. F. Schinazi. 1997. Influenza virus-inhibitory effects of a series of germanium-and silicon-centred polyoxometalates. Antivir. Chem. Chemother. 8:75-83.
18. 17a. Jakemen, K. J., and C. Sweet. Unpublished observations.
19. Kim, C. U., W. Lew, M. A. Williams, H. Liu, L. Zhang, S. Swaminathan, N. Bischofberger, M. S. Chen, D. B. Mendel, C. Y. Tai, W. G. Laver, and R. C. Stevens. 1997. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J. Am. Chem. Soc. 119:681-690.
20. Klenk, H.-D. and R. Rott. 1988. The molecular biology of influenza virus pathogenicity. Adv. Virus Res. 34:247-280.
21. Li, W., P. A. Escarpe, E. J. Eisenburg, K. C. Cundy, C. Sweet, K. J. Jakeman, J. Merson, W. Lew, M. Williams, L. Zhang, C. U. Kim, N. Bischofberger, M. S. Chen, and D. B. Mendel. 1998. Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071. Antimicrob. Agents Chemother. 42:647-653.
22. Liu, C., M. C. Eichelberger, R. W. Compans, and G. M. Air. 1995. Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding. J. Virol. 69:1099-1106.
23. Lui, K. J., and A. P. Kendal. 1987. Impact of influenza epidemics on mortality in the United States from October 1972 to May 1985. Am. J. Public Health 77:712-716.
24. Palese, P., and R. W. Compans. 1976. Inhibition of influenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA): mechanism of action. J. Gen. Virol. 33:159-163.
25. Palese, P., K. Tobita, M. Ueda, and R. W. Compans. 1974. Characterization of temperature sensitive influenza virus mutants. Virology 61:397-410.
26. Penn, C. R., J. M. Barnett, R. C. Bethell, R. Fenton, K. L. Gearing, N. Healy, and A. J. Jowett. 1996. Selection of influenza virus with reduced sensitivity in vitro to the neuraminidase inhibitor GG167 (4-guanidino-Neu5Ac2en): changes in haemagglutinin may compensate for loss of neuraminidase activity, p. 735-740. In L. E. Brown, A. W. Hampson, and R. G. Webster (ed.), Options for the control of influenza III. Elsevier, Amsterdam, The Netherlands.
27. Potier, M., L. Mameli, M. Bélisle, L. Dallaire, and S. B. Melançon. 1979. Fluorometric assay of neuraminidase with a sodium (4-methylumbelliferyl-α-D-N-acetylneuraminate) substrate. Anal. Biochem. 94:287-296.
28. Quon, C. Y., K. Mai, G. Patil, and H. F. Stampfli. 1988. Species differences in the stereoselective hydrolysis of esmol by blood esterases. Drug Metab. Dispos. 16:425-428.
29. Raut, S., J. Hurd, R. J. Cureton, G. Blandford, and R. B. Heath. 1975. The pathogenesis of infections of the mouse caused by virulent and avirulent variants of an influenza virus. J. Med. Microbiol. 8:127-136.
30. Reuman, P. D., S. Keely, and G. M. Schiff. 1989. Assessment of signs of influenza illness in the ferret model. J. Virol. Methods 24:27-34.
31. Ryan, D. M., J. Ticehurst, and M. H. Dempsey. 1995. GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is a potent inhibitor of influenza virus in ferrets. Antimicrob. Agents Chemother. 39:2583-2584.
32. Ryan, D. M., J. Ticehurst, M. H. Dempsey, and C. R. Penn. 1994. Inhibition of influenza virus replication in mice by GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is consistent with extracellular activity of viral neuraminidase (sialidase). Antimicrob. Agents Chemother. 38:2270-2275.
33. 31a. Sidwell, R. W., J. H. Huffman, D. L. Barnard, K. W. Bailey, M.-H. Wong, A. Morrison, T. Syndergaard, and C. U. Kim. Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor. Antiviral. Res., in press.
34. Sidwell, R. W., J. H. Huffman, E. W. Call, H. Alaghamandan, P. D. Cook, and R. K. Robins. 1985. Activity of selenazofurin against influenza A and B viruses in vitro. Antimicrob. Agents Chemother. 28:375-377.
35. Sidwell, R. W., J. H. Huffman, E. W. Call, et al. 1986. Effect of selenazofurin on influenza A and B virus infections of mice. Antivir. Res. 6:343-353.
36. Smith, P. W., S. L. Sollis, P. D. Howes, P. C. Cherry, K. N. Cobley, H. Taylor, A. R. Whittington, J. Scicinski, R. C. Bethell, N. Taylor, T. Skarzynski, A. Cleasby, O. Singh, A. Wonacott, J. Varghese, and P. Colman. 1996. Novel inhibitors of influenza sialidases related to GG167 structure-activity, crystallographic and molecular dynamic studies with 4H-pyran-2-carboxylic acid 6-carboxamides. Bioorg. Chem. Med. Chem. Lett. 6:2931-2936.
37. Sollis, S. L., P. W. Smith, P. D. Howes, P. C. Cherry, and R. C. Bethell. 1996. Novel inhibitors of influenza sialidase related to GG167 synthesis of 4-amino and guanidino-4H-pyran-2-carboxylic acid-6-propylamides; selective inhibitors of influenza A virus sialidase. Bioorg. Chem. Med. Chem. Lett. 6: 1805-1808.
38. Taylor, N. R., and M. von Itzstein. 1994. Molecular modeling studies on ligand binding to sialidase from influenza virus and the mechanism of catalysis. J. Med. Chem. 37:616-624.
39. Thomas, G. P., M. Forsyth, C. R. Penn, and J. W. McCauley. 1994. Inhibition of the growth of influenza viruses in vitro by 4-guanidino-2,4-dideoxy-N-acetylneuraminic acid. Antivir. Res. 24:351-356.
40. Toms, G. L., J. A. Davies, C. G. Woodward, C. Sweet, and H. Smith. 1977. The relation of pyrexia and nasal inflammatory response to virus levels in nasal washings of ferrets infected with influenza viruses of differing virulence. Br. J. Exp. Pathol. 58:444-458.
41. Varghese, J. N., J. L. McKimm-Breschkin, J. B. Caldwell, A. A. Kortt, and P. M. Colman. 1992. The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 14:327-332.
42. von Itzstein, M., W.-Y. Wu, G. B. Kok, M. S. Pegg, J. C. Cyason, B. Jin, T. V. Phan, M. L. Smythe, H. F. White, S. W. Oliver, P. M. Colman, J. N. Varghese, D. M. Ryan, J. M. Woods, R. C. Bethell, V. J. Hotham, J. M. Cameron, and C. R. Penn. 1993. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363:418-423.
43. von Itzstein, M., M. Wan Yang, and B. Jin. 1994. The synthesis of 2,3-didehydro-2,4-dideoxy-4-guanidinyl-N-acetylneuraminic acid: a potent influenza virus sialidase inhibitor. Carbohydr. Res. 259:301-305.
44. White, C. L., M. N. Janakiraman, W. G. Laver, C. Philippon, A. Vasella, G. M. Air, and M. Luo. 1995. A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies. J. Mol. Biol. 245:623-634.
45. Wood, N. D., M. Aitken, S. Sharp, and H. Evison. 1997. Tolerability and pharmacokinetics of the influenza neuraminidase inhibitor Ro 64-0802 (GS4071) following oral administration of the prodrug Ro 64-0796 (GS4104) to healthy male volunteers, Abstr. A-123, p. 25. In Program and abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
46. Woods, J. M., R. C. Bethell, J. A. V. Coates, N. Healy, S. A. Hiscox, B. A. Pearson, D. M. Ryan, J. Ticehurst, J. Tilling, S. M. Walcott, and C. R. Penn. 1993. 4-Guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of influenza A and B viruses in vitro. Antimicrob. Agents Chemother. 37:1473-1479.
47. Wyde, P. R., R. B. Couch, B. F. Mackler, T. R. Cate, and B. M. Levy. 1977. Effects of low-and high-passage influenza virus infection in normal and nude mice. Infect. Immun. 15:221-229.