Anti-influenza drugs: The development of sialidase inhibitors

Handbook of Experimental Pharmacology

Volumn 189, Issue , 2009, Pages 111-154

  Itzstein, Mark Von ^a   Thomson, Robin ^b  

^a GRIFFITH UNIVERSITY   (Australia)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

4 ACETAMIDO 5 AMINO 3 (1 ETHYLPROPOXY) 1 CYCLOHEXENE 1 CARBOXYLIC ACID; A 315675; AMANTADINE; ANTIVIRUS AGENT; BCZ 1812; CS 8958; FLUNET; OSELTAMIVIR; PERAMIVIR; R 118958; R 125489; RIMANTADINE; SIALIDASE; SIALIDASE INHIBITOR; UNCLASSIFIED DRUG; ZANAMIVIR; ENZYME INHIBITOR;

ABSENCE OF SIDE EFFECTS; ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; ASIA; CLINICAL TRIAL; CROSS RESISTANCE; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG RESEARCH; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; DRUG TOLERABILITY; ENZYME ACTIVE SITE; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME MECHANISM; ENZYME STRUCTURE; HUMAN; INFECTION CONTROL; INFECTION RATE; INFLUENZA; INFLUENZA VIRUS; INFLUENZA VIRUS A H5N1; MENTAL DISEASE; MORTALITY; NAUSEA AND VOMITING; NEUROLOGIC DISEASE; NONHUMAN; PANDEMIC; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; REVIEW; SKIN ALLERGY; SOCIAL STATUS; UNSPECIFIED SIDE EFFECT; VACCINE PRODUCTION; VIRUS GENE; VIRUS INHIBITION; VIRUS MUTATION; VIRUS PATHOGENESIS; VIRUS STRAIN; ANIMAL; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; ORTHOMYXOVIRUS;

ANIMALS; ANTIVIRAL AGENTS; DRUG DESIGN; DRUG RESISTANCE, VIRAL; ENZYME INHIBITORS; HUMANS; INFLUENZA, HUMAN; NEURAMINIDASE; ORTHOMYXOVIRIDAE; ZANAMIVIR;

EID: 61549097552     PISSN: 01712004     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-3-540-79086-0_5     Document Type: Review

References (184)

1. Abed Y, Nehmé B, Baz M, Boivin G (2008) Activity of the neuraminidase inhibitor A-315675 against oseltamivir-resistant influenza neuraminidases of N1 and N2 subtypes. Antiviral Res 77:163-166
2. Achyuthan KE, Achyuthan AM (2001) Comparative enzymology, biochemistry and pathophysiology of human exo-alpha-sialidases (neuraminidases). Compar Biochem Physiol B: Biochem Mol Biol 129:29-64
3. Air GM, Laver WG (1989) The neuraminidase of influenza virus. Proteins 6:341-356
4. Amaro RE, Minh DDL, Cheng LS, LindstromWMJr, Olson AJ, Lin J-H, LiWW, McCammon JA (2007) Remarkable loop flexibility in avian influenza N1 and its implications for antiviral drug design. J Am Chem Soc 129:7764-7765
5. Amaya MF, Watts AG, Damager I, Wehenkel A, Nguyen T, Buschiazzo A, Paris G, Frasch AC, Withers SG, Alzari PM(2004) Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase. Structure 12:775-784
6. Andrews DM, Cherry PC, Humber DC, Jones PS, Keeling SP, Martin PF, Shaw CD, Swanson S (1999) Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-guanidino- Neu5Ac2en (Zanamivir) modified in the glycerol side-chain. Eur J Med Chem 34:563-574
7. Babu YS, Chand P, Bantia S, Kotian P, Dehghani A, El-Kattan Y, Lin TH, Hutchison TL, Elliott AJ, Parker CD, Ananth SL, Horn LL, Laver GW, Montgomery JA (2000) BCX-1812 (RWJ-270201): discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design. J Med Chem 43:3482-3486
8. Baker AT, Varghese JN, Laver WG, Air GM, Colman PM (1987) Three-dimensional structure of neuraminidase of subtype N9 from an avian influenza virus. Proteins 2:111-117
9. Bamford MJ (1995) Neuraminidase inhibitors as potential anti-influenza drugs. J Enzyme Inhib 10:1-16
10. Bantia S, Parker CD, Ananth SL, Horn LL, Andries K, Chand P, Kotian PL, Dehghani A, El Kattan Y, Lin T, Hutchison TL, Montgomery JA, Kellog DL, Babu YS (2001) Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir. Antimicrob Agents Chemother 45:1162-1167
11. Bantia S, Arnold CS, Parker CD, Upshaw R, Chand P (2006) Anti-influenza virus activity of peramivir in mice with single intramuscular injection. Antiviral Res 69:39-45
12. Barroso L, Treanor J, Gubareva L, Hayden FG (2005) Efficacy and tolerability of the oral neuraminidase inhibitor peramivir in experimental human influenza: randomized, controlled trials for prophylaxis and treatment. Antiviral Ther 10:901-910
13. Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, Lochindarat S, Nguyen TKT, Nguyen TH, Tran TH, Nicoll A, Touch S, Yuen K-Y (2005) Avian influenza A (H5N1) infection in humans. N Engl J Med 353:1374-1385
14. Blick TJ, Tiong T, Sahasrabudhe A, Varghese JN, Colman PM, Hart GJ, Bethell RC, McKimm- Breschkin JL (1995) Generation and characterization of an influenza virus neuraminidase variant with decreased sensitivity to the neuraminidase-specific inhibitor 4-guanidino-Neu5Ac2en. Virology 214:475-484
15. Bossart-Whitaker P, Carson M, Babu YS, Smith CD, Laver WG, Air GM (1993) Threedimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid. J Mol Biol 232:1069-1083
16. Burmeister WP, Ruigrok RW, Cusack S (1992) The 2.2 Å resolution crystal structure of influenza B neuraminidase and its complex with sialic acid. Embo J 11:49-56
17. Burmeister WP, Henrissat B, Bosso C, Cusack S, Ruigrok RW (1993) Influenza B virus neuraminidase can synthesize its own inhibitor. Structure 1:19-26
18. Calfee DP, Hayden FG (1998) New approaches to influenza chemotherapy: neuraminidase inhibitors. Drugs 56:537-553
19. Calfee DP, Peng AW, Cass LM, Lobo M, Hayden FG (1999) Safety and efficacy of intravenous zanamivir in preventing experimental human influenza A virus infection. Antimicrob Agents Chemother 43:1616-1620
20. Carter MJ (2007) A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza. J Med Microbiol 56:875-883
21. Chan T-H, Xin Y-C, von Itzstein M (1997) Synthesis of phosphonic acid analogs of sialic acids (Neu5Ac and KDN) as potential sialidase inhibitors. J Org Chem 62:3500-3504
22. Chand P, Kotian PL, Dehghani A, El-Kattan Y, Lin T-H, Hutchison TL, Babu YS, Bantia S, Elliott AJ, Montgomery JA (2001) Systematic structure-based design and stereoselective synthesis of novel multisubstituted cyclopentane derivatives with potent antiinfluenza activity. J Med Chem 44:4379-4392
23. Chand P, Babu YS, Bantia S, Rowland S, Dehghani A, Kotian PL, Hutchison TL, Ali S, Brouillette W, El-Kattan Y, Lin T-H (2004) Syntheses and neuraminidase inhibitory activity of multisubstituted cyclopentane amide derivatives. J Med Chem 47:1919-1929
24. Chand P, Bantia S, Kotian PL, El-Kattan Y, Lin T-H, Babu YS (2005a) Comparison of the antiinfluenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo. Bioorg Med Chem 13:4071-4077
25. Chand P, Kotian PL, Morris PE, Bantia S, Walsh DA, Babu YS (2005b) Synthesis and inhibitory activity of benzoic acid and pyridine derivatives on influenza neuraminidase. BioorgMed Chem 13:2665-2678
26. Chavas LMG, Tringali C, Fusi P, Venerando B, Tettamanti G, Kato R, Monti E,Wakatsuki S (2005) Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic nature of substrate recognition. J Biol Chem 280:469-475
27. Chong AK, Pegg MS, Taylor NR, von Itzstein M (1992) Evidence for a sialosyl cation transitionstate complex in the reaction of sialidase from influenza virus. Eur J Biochem 207:335-343
28. Cinatl J Jr, Michaelis M, Doerr HW (2007a) The threat of avian influenza A (H5N1). III. Antiviral therapy. Med Microbiol Immunol 196:203-212
29. Cinatl J Jr, Michaelis M, Doerr HW(2007b) The threat of avian influenza A (H5N1). IV. Development of vaccines. Med Microbiol Immunol 196:213-225
30. Colman PM (1994) Influenza virus neuraminidase: structure, antibodies, and inhibitors. Protein Sci 3:1687-1696
31. Colman PM, Ward CW (1985) Structure and diversity of influenza virus neuraminidase. Curr Top Microbiol Immunol 114:177-255
32. Colman PM, Varghese JN, Laver WG (1983) Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 303:41-44
33. Corfield AP, Schauer R (1982) Metabolism of sialic acids. In: Schauer R (ed) Sialic acids - Chemistry, metabolism and function. Springer, Wien, pp 195-261
34. Corfield AP, Higa H, Paulson JC, Schauer R (1983) The specificity of viral and bacterial sialidases for alpha(2-3)- and alpha(2-6)-linked sialic acids in glycoproteins. Biochim Biophys Acta 744:121-126
35. Couceiro JN, Paulson JC, Baum LG (1993) Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of hemagglutinin receptor specificity. Virus Res 29:155-165
36. De Clercq E, Neyts J (2007) Avian influenza A (H5N1) infection: targets and strategies for chemotherapeutic intervention. Trends Pharmacol Sci 28:280-285
37. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJD, Chau TNB, Hoang DM, Nguyen VVC, Khanh TH, Dong VC, Qui PT, Van Cam B, Ha DQ, Guan Y, Peiris JSM, Chinh NT, Hien TT, Farrar J (2006) Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nature Med 12:1203-1207
38. Doucette KE, Aoki FY (2001) Oseltamivir: a clinical and pharmacological perspective. Expert Opin Pharmacother 2:1671-1683
39. Douglas RGJ (1990) Drug therapy, prophylaxis and treament of influenza. N Engl J Med 322:443-450
40. Edmond JD, Johnston RG, Kidd D, Rylance HJ, Sommerville RG (1966) The inhibition of neuraminidase and antiviral action. Br J Pharmac Chemother 27:415-426
41. Eisenberg EJ, Bidgood A, Cundy KC (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
42. El Ashry ESH, Rashed N, Shobier AHS (2000) Glycosidase inhibitors and their chemotherapeutic value, part 2. Pharmazie 55:331-348
43. Ferraris O, Kessler N, Lina B (2005) Sensitivity of influenza viruses to zanamivir and oseltamivir: a study performed on viruses circulating in France prior to the introduction of neuraminidase inhibitors in clinical practice. Antiviral Res 68:43-48
44. Fleming DM(2003) Zanamivir in the treatment of influenza. Expert Opin Pharmacother 4:799-805
45. Goodford PJ (1985) A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. J Med Chem 28:849-857
46. Gottschalk A (1958) Neuraminidase; its substrate and mode of action. Adv Enzymol 20:135-146
47. Govorkova EA, Leneva IA, Goloubeva OG, Bush K, Webster RG (2001) Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob Agents Chemother 45:2723-2732
48. Govorkova EA, Fang H-B, Tan M, Webster RG (2004) Neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in MDCK cells. Antimicrob Agents Chemother 48:4855-4863
49. Gubareva LV (2004) Molecular mechanisms of influenza virus resistance to neuraminidase inhibitors. Virus Res 103:199-203
50. Gubareva LV, Robinson MJ, Bethell RC,Webster RG (1997) Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en. J Virol 71:3385-3390
51. Gubareva LV, Matrosovich MN, Brenner MK, Bethell RC, Webster RG (1998) Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. J Infect Dis 178:1257-1262
52. Gubareva LV, Kaiser L, Matrosovich MN, Soo-Hoo Y, Hayden FG (2001) Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis 183:523-531
53. Hagiwara T, Kijima-Suda I, Ido T, Ohrui H, Tomita K (1994) Inhibition of bacterial and viral sialidases by 3-fluoro-N-acetylneuraminic acid. Carbohydr Res 263:167-172
54. Haskell TH, Peterson FE, Watson D, Plessas NR, Culbertson T (1970) Neuraminidase inhibition and viral chemotherapy. J Med Chem 13:697-704
55. Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, Kawaoka Y (2007) Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. JAMA 297:1435-1442
56. Hay AJ (1992) The action of adamantanamines against influenza A viruses: inhibition of the M2 ion channel protein. Semin Virol 3:21-30
57. Hay AJ, Thompson CA, Geraghty A, Hayhurst S, Grambas S, Bennett MS (1993) The role of the M2 protein in influenza virus infection. In: Hannoun C (ed) Options for the control of influenza virus, vol II. Excerpta Medica, Amsterdam, pp 281-288
58. He G, Massarella J, Ward P (1999) Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet 37:471-484
59. Herrler G, Hausmann J, Klenk H-D (1995) Sialic acid as receptor determinant of ortho- and paramyxoviruses. In: Rosenberg A (ed) Biology of the sialic acids. Plenum, NY, pp 315-336
60. Holzer CT, von Itzstein M, Jin B, Pegg MS, Stewart WP, Wu WY (1993) Inhibition of sialidases from viral, bacterial and mammalian sources by analogues of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid modified at the C-4 position. Glycoconj J 10:40-44
61. Honda T, Masuda T, Yoshida S, Arai M, Kaneko S, Yamashita M (2002a) Synthesis and anti- Influenza virus activity of 7-O-Alkylated derivatives related to zanamivir. Bioorg Med Chem Lett 12:1925-1928
62. Honda T, Masuda T, Yoshida S, Arai M, Kobayashi Y, Yamashita M (2002b) Synthesis and anti-influenza virus activity of 4-guanidino-7-substituted Neu5Ac2en derivatives. Bioorg Med Chem Lett 12:1921-1924
63. Honda T, Yoshida S, Arai M, Masuda T, Yamashita M (2002) Synthesis and anti-influenza evaluation of polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives. Bioorg Med Chem Lett 12:1929-1932
64. Hurt AC, Iannello P, Jachno K, Komadina N, Hampson AW, Barr IG, McKimm-Breschkin JL (2006) Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient. Antimicrob Agents Chemother 50:1872-1874
65. Hurt AC, Selleck P, Komadina N, Shaw R, Brown L, Barr IG (2007) Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes. Antiviral Res 73:228-231
66. Ilyushina NA, Bovin NV, Webster RG, Govorkova EA (2006) Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 70:121-131
67. Islam T, von Itzstein M (2007) Anti-influenza drug discovery: are we ready for the next pandemic? Adv Carbohydr Chem Biochem 61:293-352
68. Ison MG, Gubareva LV, Atmar RL, Treanor J, Hayden FG (2006a) Recovery of drug-resistant influenza virus from immunocompromised patients: a case series. J Infect Dis 193:760-764
69. Ison MG, Mishin VP, Braciale TJ, Hayden FG, Gubareva LV (2006b) Comparative activities of oseltamivir and A-322278 in immunocompetent and immunocompromised murine models of influenza virus infection. J Infect Dis 193:765-772
70. Ives JA, Carr JA, Mendel DB, Tai CY, Lambkin R, Kelly L, Oxford JS, Hayden FG, Roberts NA (2002) The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res 55:307-317
71. Kati WM, Montgomery D, Maring C, Stoll VS, Giranda V, Chen X, Laver WG, Kohlbrenner W, Norbeck DW (2001) Novel alpha- and beta-amino acid inhibitors of influenza virus neuraminidase. Antimicrob Agents Chemother 45:2563-2570
72. Kati WM, Montgomery D, Carrick R, Gubareva L, Maring C, McDaniel K, Steffy K, Molla A, Hayden F, Kempf D, Kohlbrenner W (2002) In vitro characterization of A-315675, a highly potent inhibitor of A and B strain influenza virus neuraminidases and influenza virus replication. Antimicrob Agents Chemother 46:1014-1021
73. Khorlin AY, Privalova IM, Zakstelskaya LY, Molibog EV, Evstigneeva NA (1970) Synthetic inhibitors of Vibrio cholerae neuraminidase and neuraminidases of some influenza virus strains. FEBS Lett 8:17-19
74. Kim CU, Lew W, Williams MA, Liu H, Zhang L, Swaminathan S, Bischofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC (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
75. Kim CU, Lew W, Williams MA, Wu H, Zhang L, Chen X, Escarpe PA, Mendel DB, Laver WG, Stevens RC (1998) Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors. J Med Chem 41:2451-2460
76. Kim CU, Chen X, Mendel DB (1999) Neuraminidase inhibitors as anti-influenza virus agents. Antiviral Chem Chemother 10:141-154
77. Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y (2004) Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 364:759-765
78. Klumpp K (2004) Recent advances in the discovery and development of anti-influenza drugs. Exp Opin Ther Patents 14:1153-1168
79. Kuszewski K, Brydak L (2000) The epidemiology and history of influenza. Biomed Pharmacother 54:188-195
80. Laver G, Garman E (2002) Pandemic influenza: its origin and control. Microbes Infect 4:1309-1316
81. Le QM, Kiso M, Someya K, Sakai YT, Nguyen TH, Nguyen KHL, Pham ND, Ngyen HH, Yamada S, Muramoto Y, Horimoto T, Takada A, Goto H, Suzuki T, Suzuki Y, Kawaoka Y (2005) Avian flu: isolation of drug-resistant H5N1 virus. Nature 437:1108
82. Lew W, Chen X, Kim CU (2000) Discovery and development of GS 4104 (oseltamivir): an orally active influenza neuraminidase inhibitor. Curr Med Chem 7:663-672
83. Li C-Y, Yu Q, Ye Z-Q, Sun Y, He Q, Li X-M, Zhang W, Luo J, Gu X, Zheng X, Wei L (2007) A nonsynonymous SNP in human cytosolic sialidase in a small Asian population results in reduced enzyme activity: potential link with severe adverse reactions to oseltamivir. Cell Res 17:357-362
84. Lillelund VH, Jensen HH, Liang X, Bols M (2002) Recent developments of transition-state analogue glycosidase inhibitors of non-natural product origin. Chem Rev 102:515-553
85. Liu Z-Y, Wang B, Zhao L-X, Li Y-H, Shao H-Y, Yi H, You X-F, Li Z-R (2007) Synthesis and anti-influenza activities of carboxyl alkoxyalkyl esters of 4-guanidino-Neu5Ac2en (zanamivir). Bioorg Med Chem Lett 17:4851-4854
86. Ly HD, Withers SG (1999) Mutagenesis of glycosidases. Annu Rev Biochem 68:487-522
87. Macdonald SJ, Watson KG, Cameron R, Chalmers DK, Demaine DA, Fenton RJ, Gower D, Hamblin JN, Hamilton S, Hart GJ, Inglis GGA, Jin B, Jones HT, McConnell DB, Mason AM, Nguyen V, Owens IJ, Parry N, Reece PA, Shanahan SE, Smith D, Wu W-Y, Tucker SP (2004) Potent and long-acting dimeric inhibitors of influenza virus neuraminidase are effective at a once-weekly dosing regimen. Antimicrob Agents Chemother 48:4542-4549
88. Macdonald SJ, Cameron R, Demaine DA, Fenton RJ, Foster G, Gower D, Hamblin JN, Hamilton S, Hart GJ, Hill AP, Inglis GGA, Jin B, Jones HT, McConnell DB,McKimm-Breschkin J,Mills G, Nguyen V, Owens IJ, Parry N, Shanahan SE, Smith D,Watson KG,WuW-Y, Tucker SP (2005) Dimeric zanamivir conjugates with various linking groups are potent, long-lasting inhibitors of influenza neuraminidase including H5N1 avian influenza. J Med Chem 48:2964-2971
89. Maring CJ, Stoll VS, Zhao C, Sun M, Krueger AC, Stewart KD, Madigan DL, Kati WM, Xu Y, Carrick RJ, Montgomery DA, Kempf-Grote A, Marsh KC, Molla A, Steffy KR, Sham HL, Laver WG, Gu Y-G, Kempf DJ, Kohlbrenner WE (2005) Structure-based characterization and optimization of novel hydrophobic binding interactions in a series of pyrrolidine influenza neuraminidase inhibitors. J Med Chem 48:3980-3990
90. Masuda T, Shibuya S, Arai M, Yoshida S, Tomozawa T, Ohno A, Yamashita M, Honda T (2003a) Synthesis and anti-influenza evaluation of orally active bicyclic ether derivatives related to zanamivir. Bioorg Med Chem Lett 13:669-673
91. Masuda T, Yoshida S, Arai M, Kaneko S, Yamashita M, Honda T (2003b) Synthesis and antiinfluenza evaluation of polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives. Chem Pharm Bull (Tokyo) 51:1386-1398
92. Matrosovich M, Klenk H-D (2003) Natural and synthetic sialic acid-containing inhibitors of influenza virus receptor binding. Rev Med Virol 13:85-97
93. Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk H-D (2004) Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J Virol 78:12665-12667
94. McCullers JA (2005) Antiviral therapy of influenza. Expert Opin Investig Drugs 14:305-312
95. McCullers JA (2006) The clinical need for new antiviral drugs directed against influenza virus. J Infect Dis 193:751-753
96. McKimm-Breschkin JL (2000) Resistance of influenza viruses to neuraminidase inhibitors - a review. Antiviral Res 47:1-17
97. Meanwell NA, Krystal M (1996a) Taking aim at a moving target - inhibitors of influenza virus. I. Virus adsorption, entry and uncoating. Drug Disc Today 1:316-324
98. Meanwell NA, Krystal M (1996b) Taking aim at a moving target - inhibitors of influenza virus. II. Viral replication, packaging and release. Drug Disc Today 1:388-397
99. Meindl P, Tuppy H (1969) 2-Deoxy-2,3-dehydrosialic acids. II. Competitive inhibition of Vibrio cholerae neuraminidase by 2-deoxy-2,3-dehydro-N- acylneuraminic acids. Hoppe-Seyler's Z Physiol Chem 350:1088-1092
100. Meindl P, Bodo G, Palese P, Schulman J, Tuppy H (1974) Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N- acetylneuraminic acid. Virology 58:457-463
101. Mendel DB, Tai CY, Escarpe PA, LiW, Sidwell RW, Huffman JH, Sweet C, Jakeman KJ, Merson J, Lacy SA, Lew W, Williams MA, Zhang L, Chen MS, Bischofberger N, Kim CU (1998) Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection. Antimicrob Agents Chemother 42:640-646
102. Miller CA, Wang P, Flashner M (1978) Mechanism of Arthrobacter sialophilus neuraminidase: the binding of substrates and transition-state analogs. Biochem Biophys Res Commun 83:1479-1487
103. Mishin VP, Hayden FG, Gubareva LV (2005) Susceptibilities of antiviral-resistant influenza viruses to novel neuraminidase inhibitors. Antimicrob Agents Chemother 49:4515-4520
104. Molla A, Kati W, Carrick R, Steffy K, Shi Y, Montgomery D, Gusick N, Stoll VS, Stewart KD, Ng TI, Maring C, Kempf DJ, Kohlbrenner W (2002) In vitro selection and characterization of influenza A. (A/N9) virus variants resistant to a novel neuraminidase inhibitor, A-315675. J Virol 76:5380-5386
105. Monti E, Bassi MT, Bresciani R, Civini S, Croci GL, Papini N, Riboni M, Zanchetti G, Ballabio A, Preti A, Tettamanti G, Venerando B, Borsani G (2004) Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family. Genomics 83:445-453
106. Monto AS, McKimm-Breschkin JL, Macken C, Hampson AW, Hay A, Klimov A, Tashiro M, Webster RG, Aymard M, Hayden FG, Zambon M (2006) Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their use. Antimicrob Agents Chemother 50:2395-2402
107. Moscona A (2005) Oseltamivir resistance - disabling our influenza defenses. N Engl J Med 353:2633-2636
108. Nöhle U, Beau JM, Schauer R (1982) Uptake, metabolism and excretion of orally and intravenously administered, double-labeled N-glycoloylneuraminic acid and single-labeled 2-deoxy- 2,3-dehydro-N-acetylneuraminic acid in mouse and rat. Eur J Biochem 126:543-548
109. Oxford J (2005) Oseltamivir in the management of influenza. Expert Opin Pharmacother 6:2493-2500
110. Oxford JS (2000) Zanamivir (Glaxo Wellcome). IDrugs 3:447-459
111. Palese P, Compans RW (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
112. Palese P, Schulman JL (1977) Inhibitors of viral neuraminidase as potential antiviral drugs. In: Oxford JS (ed) Chemoprophylaxis and viral infection of the upper respiratory tract, vol 1. CRC, Cleveland, Ohio, pp 189-202
113. Palese P, Schulman JL, Bodo G, Meindl P (1974a) Inhibition of influenza and parainfluenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N- trifluoroacetylneuraminic acid (FANA). Virology 59:490-498
114. Palese P, Tobita K, Ueda M, Compans RW (1974b) Characterization of temperature sensitive influenza virus mutants defective in neuraminidase. Virology 61:397-410
115. Pegg MS, von Itzstein M (1994) Slow-binding inhibition of sialidase from influenza virus. Biochem Mol Biol Int 32:851-858
116. Pinto LH, Holsinger LJ, Lamb RA (1992) Influenza virus M2 protein has ion channel activity. Cell 69:517-528
117. Rameix-Welti MA, Agou F, Buchy P, Mardy S, Aubin JT, Véron M, van der Werf S, Naffakh N (2006) Natural variation can significantly alter the sensitivity of influenza A (H5N1) viruses to oseltamivir. Antimicrob Agents Chemother 50:3809-3815
118. Rameix-Welti MA, Enouf V, Cuvelier F, Jeannin P, van der Werf S (2008) Enzymatic properties of the neuraminidase of seasonal H1N1 influenza viruses provide insights for the emergence of natural resistance to oseltamivir. PLoS Pathog. 2008 Jul 25;4(7):e1000103
119. Reece PA (2007) Neuraminidase inhibitor resistance in influenza viruses. J Med Virol 79:1577-1586
120. Rich JR, Gehle D, von Itzstein M (2007) Design and synthesis of sialidase inhibitors for influenza virus infections. In: Kamerling JP, Boons G-J, Lee YC, Suzuki A, Tanigichi N, Voragen AGJ (eds) Comprehensive glycoscience. Elsevier, Oxford, pp 885-922
121. Röhm C, Zhou N, Süss J, Mackenzie J, Webster RG (1996) Characterization of a novel influenza hemagglutinin, H15: criteria for determination of influenza A subtypes. Virology 217:508-516
122. Russell RJ, Haire LF, Stevens DJ, Collins PJ, Lin YP, Blackburn GM, Hay AJ, Gamblin SJ, Skehel JJ (2006) The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 443:45-49
123. Ryan DM, Ticehurst J, Dempsey M, Penn CR (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 actiivity of viral neuraminidase (sialidase). Antimicrob Agents Chemother 10:2270-2275
124. Ryan DM, Ticehurst J, Dempsey MH (1995) GG167 (4-guanidino-2,4-dideoxy-2, 3-dehydro-Nacetylneuraminic acid) is a potent inhibitor of influenza virus in ferrets. Antimicrob Agents Chemother 39:2583-2584
125. Rye CS, Withers SG (2000) Glycosidase mechanisms. Curr Opin Chem Biol 4:573-580
126. Saito M, Yu RK (1995) Biochemistry and function of sialidases. In: Rosenberg A (ed) Biology of the sialic acids. Plenum, NY, pp 261-313
127. Sheu TG, Deyde VM, Okomo-Adhiambo M, Garten RJ, Xu X, Bright RA, Butler EN, Wallis TR, Klimov AI, Gubareva LV (2008) Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008. Antimicrob Agents Chemother 52:3284-3292.
128. Shi D, Yang J, Yang D, LeCluyse EL, Black C, You L, Akhlaghi F, Yan B (2006) Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther 319:1477-1484
129. Shie J-J, Fang J-M, Wang S-Y, Tsai K-C, Cheng Y-SE, Yang A-S, Hsiao S-C, Su C-Y, Wong C-H (2007) Synthesis of Tamiflu and its phosphonate congeners possessing potent anti-influenza activity. J Am Chem Soc 129:11892-11893
130. Sidwell RW, Smee DF (2002) Peramivir (BCX-1812, RWJ-270201): potential new therapy for influenza. Exp Opin Investig Drugs 11:859-869
131. Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Ann Rev Biochem 69:531-569
132. Smee DF, Huffman JH, Morrison AC, Barnard DL, Sidwell RW (2001) Cyclopentane neuraminidase inhibitors with potent in vitro anti-influenza virus activities. Antimicrob Agents Chemother 45:743-748
133. Smee DF, Bailey KW, Morrison AC, Sidwell RW (2002) Combination treatment of influenza A virus infections in cell culture and in mice with the cyclopentane neuraminidase inhibitor RWJ-270201 and ribavirin. Chemotherapy 48:88-93
134. Smith FI, Palese P (1989) Variation in the influenza virus genes: epidemiological, pathogenic and evolutionary consequences. In: Krug RM (ed) The influenza viruses. Plenum, NY, pp 319-350
135. Smith PW, Sollis SL, Howes PD, Cherry PC, Cobley KN, Taylor H, Whittington AR, Scicinski J, Bethell RC, Taylor N, Skarzynski T, Cleasby A, Singh O, Wonacott A, Varghese J, Colman P (1996) Novel inhibitors of influenza sialidases related to GG167. Structure-actvity, crystallographic and molecular dynamics studies with 4-H-pyran-2-carboxylic acid 6-carboxamides. Bioorg Med Chem Lett 6:2931-2936
136. Smith BJ, Colman PM, von Itzstein M, Danylec B, Varghese JN (2001) Analysis of inhibitor binding in influenza virus neuraminidase. Protein Sci 10:689-696
137. Smith BJ, McKimm-Breshkin JL, McDonald M, Fernley RT, Varghese JN, Colman PM (2002) Structural studies of the resistance of influenza virus neuraminidase to inhibitors. J Med Chem 45:2207-2212
138. Smith PW, Sollis SL, Howes PD, Cherry PC, Starkey ID, Cobley KN, Weston H, Scicinski J, Merritt A, Whittington A, Wyatt P, Taylor N, Green D, Bethell R, Madar S, Fenton RJ, Morley PJ, Pateman T, Beresford A (1998) Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. I. Discovery, synthesis, biological activity, and structure-activity relationships of 4-guanidino- and 4-amino-4H-pyran-6- carboxamides. J Med Chem 41:787-797
139. Stoll V, Stewart KD, Maring CJ, Muchmore S, Giranda V, Gu Y-GY, Wang G, Chen Y, Sun M, Zhao C, Kennedy AL, Madigan DL, Xu Y, Saldivar A, Kati W, Laver G, Sowin T, Sham HL, Greer J, Kempf D (2003) Influenza neuraminidase inhibitors: structure-based design of a novel inhibitor series. Biochemistry 42:718-727
140. Sun X-L (2007) Recent anti-influenza strategies in multivalent sialyloligosaccharides and sialylmimetics approaches. Curr Med Chem 14:2304-2313
141. Suzuki Y, Sato K, Kiso M, Hasegawa A (1990) New ganglioside analogs that inhibit influenza virus sialidase. Glycoconj J 7:349-356
142. Suzuki Y, Ito T, Suzuki T, Holland RE Jr, Chambers TM, Kiso M, Ishida H, Kawaoka Y (2000) Sialic acid species as a determinant of the host range of influenza A viruses. J Virol 74:11825-11831
143. Taubenberger JK, Reid AH, Fanning TG (2000) The 1918 influenza virus: a killer comes into view. Virology 274:241-245
144. Taylor NR, von Itzstein M (1994) Molecular modeling studies on ligand binding to sialidase from influenza virus and the mechanism of catalysis. J Med Chem 37:616-624
145. Taylor NR, Cleasby A, Singh O, Skarzynski T, Wonacott AJ, Smith PW, Sollis SL, Howes PD, Cherry PC, Bethell R, Colman P, Varghese J (1998) Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus types A and B. J Med Chem 41:798-807
146. Thomas A, Jourand D, Bret C, Amara P, Field MJ (1999) Is there a covalent intermediate in the viral neuraminidase reaction? A hybrid potential free-energy study. J Am Chem Soc 121:9693-9702
147. Tisdale M (2000) Monitoring of viral susceptibility: new challenges with the development of influenza NA inhibitors. Rev Med Virol 10:45-55
148. Varghese JN, Colman PM (1991) Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 Å resolution. J Mol Biol 221:473-486
149. Varghese JN, Laver WG, Colman PM (1983) Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution. Nature 303:35-40
150. Varghese JN,McKimm-Breschkin JL, Caldwell JB, Kortt AA, Colman PM (1992) The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 14:327-332
151. Varghese JN, Smith PW, Sollis SL, Blick TJ, Sahasrabudhe A, McKimmBreschkin JL, Colman PM (1998) Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase. Structure 6:735-746
152. von Itzstein M, Wu WY, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, Colman PM, Varghese JN, Ryan DM, Woods JM, Bethell RC, Hotham VJ, Cameron JM, Penn CR (1993) Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363:418-423
153. von Itzstein M, Dyason JC, Oliver SW, White HF, Wu W-Y, Kok GB, Pegg MS (1996) A study of the active site of influenza virus sialidase: an approach to the rational design of novel antiinfluenza drugs. J Med Chem 39:388-391
154. von ItzsteinM(2007) The war against influenza: discovery and development of sialidase inhibitors. Nature Rev Drug Discov 6:967-974
155. von Itzstein M (2008) Avian influenza virus, a very sticky situation. Curr Opin Chem Biol 12:102-108.
156. Vorwerk S, Vasella A (1998) Carbocyclic analogs of N-acetyl-2,3- didehydro-2-deoxy-Dneuraminic acid (Neu5Ac2en, DANA): synthesis and inhibition of viral and bacterial neuraminidases. Angew Chem Int Ed 37:1732-1734
157. Wade RC (1997) 'Flu' and structure-based drug design. Structure 5:1139-1145
158. Wagner R, Matrosovich M, Klenk H-D (2002) Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol 12:159-166
159. Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127-134
160. Walop JN, Boschman TAC, Jacobs J (1960) Affinity of N-acetylneuraminic acid for influenza virus neuraminidase. Biochim Biophys Acta 44:185-186
161. Wang GT (2002) Recent advances in the discovery and development of anti-influenza drugs. Exp Opin Ther Patents 12:845-861
162. Wang GT, Chen Y, Wang S, Gentles R, Sowin T, Kati W, Muchmore S, Giranda V, Stewart K, Sham H, Kempf D, Laver WG (2001) Design, synthesis, and structural analysis of influenza neuraminidase inhibitors containing pyrrolidine cores. J Med Chem 44:1192-1201
163. Wang GT, Wang S, Gentles R, Sowin T, Maring CJ, Kempf DJ, Kati WM, Stoll V, Stewart KD, Laver G (2005) Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core. Bioorg Med Chem Lett 15:125-128
164. Wang MZ, Tai CY, Mendel DB (2002) Mechanism by which mutations at His274 alter sensitivity of influenza a virus N1 neuraminidase to oseltamivir carboxylate and zanamivir. Antimicrob Agents Chemother 46:3809-3816
165. Wang S-Q, Du Q-S, Chou K-C (2007) Study of drug resistance of chicken influenza A virus (H5N1) from homology-modeled 3D structures of neuraminidases. Biochem Biophys Res Commun 354:634-640
166. Watson JN, Dookhun V, Borgford TJ, Bennet AJ (2003) Mutagenesis of the conserved active-site tyrosine changes a retaining sialidase into an inverting sialidase. Biochemistry 42:12682-12690
167. Watson JN, Newstead S, Narine AA, Taylor G, Bennet AJ (2005) Two nucleophilic mutants of the Micromonospora viridifaciens sialidase operate with retention of configuration by two different mechanisms. Chembiochem 6:1999-2004
168. Watson KG, Cameron R, Fenton RJ, Gower D, Hamilton S, Jin B, Krippner GY, Luttick A, McConnell D, MacDonald SJ,Mason AM, Nguyen V, Tucker SP,WuWY(2004) Highly potent and long-acting trimeric and tetrameric inhibitors of influenza virus neuraminidase. Bioorg Med Chem Lett 14:1589-1592
169. Watts AG, Withers SG (2004) The synthesis of some mechanistic probes for sialic acid processing enzymes and the labeling of a sialidase from Trypanosoma rangeli. Can J Chem 82:1581-1588
170. Watts AG, Oppezzo P,Withers SG, Alzari PM, Buschiazzo A (2006) Structural and kinetic analysis of two covalent sialosyl-enzyme intermediates on Trypanosoma rangeli sialidase. J Biol Chem 281:4149-4155
171. Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y (1992) Evolution and ecology of influenza A viruses. Microbiol Mol Biol Rev 56:152-179
172. Webster RG, Shortridge KF, Kawaoka Y (1997) Influenza: interspecies transmission and emergence of new pandemics. FEMS Immunol Med Microbiol 18:275-279
173. White CL, Janakiraman MN, Laver WG, Philippon C, Vasella A, Air GM, Luo M (1995) A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies. J Mol Biol 245:623-634
174. Wintermeyer SM, Nahata MC (1995) Rimantidine: a clinical perspective. Ann Pharmacother 29:299-310
175. Woods JM, Bethell RC, Coates JAV, Healy N, Hiscox SA, Pearson BA, Ryan DM, Ticehurst J, Tilling J, Walcott SM, Penn CR (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 influenza-B viruses in vitro. Antimicrob Agents Chemother 37:1473-1479
176. Wyatt PG, Coomber BA, Evans DN, Jack TI, Fulton HE, Wonacott AJ, Colman P, Varghese J (2001) Sialidase inhibitors related to zanamivir. Further SAR studies of 4-amino-4H-pyran-2- carboxylic acid-6-propylamides. Bioorg Med Chem Lett 11:669-673
177. Yamamoto T, Kumazawa H, Inami K, Teshima T, Shiba T (1992) Syntheses of sialic acid isomers with inhibitory activity against neuraminidase. Tetrahedron Lett 33:5791-5794
178. Yamashita M (2004) R-118958, a unique anti-influenza agent showing high efficacy for both prophylaxis and treatment after a single administration: from the in vitro stage to phase I study. Int Congress Ser 1263:38-42
179. Yamashita M, Ohno A, Tomozawa T, Yoshida S (2003) R-118958, a unique anti-influenza agent. I. A prodrug form of R-125489, a novel inhibitor of influenza virus neuraminidase. In: 43rd interscience conference on antimicrobial agents and chemotherapy, Chicago, USA, Sept 14-17, Poster F-1829
180. Yen H-L, Herlocher LM, Hoffmann E, Matrosovich MN, Monto AS, Webster RG, Govorkova EA (2005) Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob Agents Chemother 49:4075-4084
181. Zambon M, Hayden FG (2001) Position statement: global neuraminidase inhibitor susceptibility network. Antiviral Res 49:147-156
182. Zechel DL, Withers SG (2001) Dissection of nucleophilic and acid-base catalysis in glycosidases. Curr Opin Chem Biol 5:643-649
183. Zhang J, Yu K, ZhuW, Jiang H (2006) Neuraminidase pharmacophore model derived from diverse classes of inhibitors. Bioorg Med Chem Lett 16:3009-3014
184. Zürcher T, Yates PJ, Daly J, Sahasrabudhe A, Walters M, Dash L, Tisdale M, McKimm-Breschkin JL (2006) Mutations conferring zanamivir resistance in human influenza virus N2 neuraminidases compromise virus fitness and are not stably maintained in vitro. J Antimicrob Chemother 58:723-732