Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance

Influenza and other Respiratory Viruses

Volumn 7, Issue 1 SUPPL.1, 2013, Pages 25-36

  Mckimm Breschkin, Jennifer L ^a  

^a CSIRO   (Australia)

Author keywords

Influenza; M2 inhibitors; Oseltamivir; Peramivir; Resistance; Zanamivir

Indexed keywords

LANINAMIVIR; OSELTAMIVIR; PERAMIVIR; ZANAMIVIR;

ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; BINDING AFFINITY; DRUG BINDING; DRUG BLOOD LEVEL; DRUG SENSITIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; IC 50; INFLUENZA; INFLUENZA A (H1N1); INFLUENZA A (H3N2); INFLUENZA A (H5N1); INFLUENZA B; INFLUENZA VIRUS A H1N1; INFLUENZA VIRUS A H3N2; INFLUENZA VIRUS A H5N1; INFLUENZA VIRUS B; NONHUMAN; PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE; VIRUS MUTATION; VIRUS STRAIN;

ANTIVIRAL AGENTS; DRUG RESISTANCE, VIRAL; ENZYME INHIBITORS; HUMANS; INFLUENZA A VIRUS, H1N1 SUBTYPE; INFLUENZA A VIRUS, H3N2 SUBTYPE; INFLUENZA A VIRUS, H5N1 SUBTYPE; INFLUENZA B VIRUS; INFLUENZA, HUMAN; NEURAMINIDASE;

EID: 84871833125     PISSN: 17502640     EISSN: 17502659     Source Type: Journal    
DOI: 10.1111/irv.12047     Document Type: Review

References (115)

1. Rosenberg MR, Casarotto MG. Coexistence of two adamantane binding sites in the influenza A M2 ion channel. Proc Natl Acad Sci USA 2010; 107:13866-13871.
2. Davies WL, Grunert RR, Haff RF et al. Antiviral Activity of 1-Adamantanamine (Amantadine). Science 1964; 144:862-863.
3. Monto AS. Antivirals and influenza: frequency of resistance. Pediatr Infect Dis J 2008; 27:S110-S112.
4. Gubareva LV, Trujillo AA, Okomo-Adhiambo M et al. Comprehensive assessment of 2009 pandemic influenza A (H1N1) virus drug susceptibility in vitro. Antivir Ther 2010; 15:1151-1159.
5. Saito R, Suzuki Y, Li D et al. Increased incidence of adamantane-resistant influenza A(H1N1) and A(H3N2) viruses during the 2006-2007 influenza season in Japan. J Infect Dis 2008; 197:630-632; author reply 632-633
6. Bright RA, Shay DK, Shu B, Cox NJ, Klimov AI. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA 2006; 295:891-894.
7. Hurt AC, Selleck P, Komadina N et al. Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes. Antiviral Res 2007; 73:228-231.
8. Cheung CL, Rayner JM, Smith GJ et al. Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis 2006; 193:1626-1629.
9. Von Itzstein M, Wu WY, Kok GB et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993; 363:418-423.
10. Kim CU, Lew W, Williams MA et al. 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 1997; 119:681-690.
11. Varghese JN, McKimm-Breschkin JL, Caldwell JB, Kortt AA, Colman PM. The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 1992; 14:327-332.
12. Babu YS, Chand P, Bantia S et al. 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 2000; 43:3482-3486.
13. Koyama K, Takahashi M, Nakai N et al. Pharmacokinetics and disposition of CS-8958, a long-acting prodrug of the novel neuraminidase inhibitor laninamivir in rats. Xenobiotica 2010; 40:207-216.
14. Potier M, Mameli L, Belisle M, Dallaire L, Melancon SB. Fluorometric assay of neuraminidase with a sodium (4-methylumbelliferyl- alpha-D-N-acetylneuraminate) substrate. Anal Biochem 1979; 94:287-296.
15. Buxton RC, Edwards B, Juo RR et al. Development of a sensitive chemiluminescent neuraminidase assay for the determination of influenza virus susceptibility to zanamivir. Anal Biochem 2000; 280:291-300.
16. McKimm-Breschkin J, Trivedi T, Hampson A et al. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother 2003; 47:2264-2272.
17. Wetherall NT, Trivedi T, Zeller J et al. Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the Neuraminidase Inhibitor Susceptibility Network. J Clin Microbiol 2003; 41:742-750.
18. Tashiro M, McKimm-Breschkin JL, Saito T et al. Surveillance for neuraminidase-inhibitor-resistant influenza viruses in Japan, 1996-2007. Antivir Ther 2009; 14:751-761.
19. Oo C, Barrett J, Hill G et al. Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children. Paediatr Drugs 2001; 3:229-236. [erratum appears in Paediatric Drugs 2001;3(4):246]
20. Morrison D, Roy S, Rayner C et al. A randomized, crossover study to evaluate the pharmacokinetics of amantadine and oseltamivir administered alone and in combination. PLoS ONE 2007; 2:e1305.
21. Wattanagoon Y, Stepniewska K, Lindegardh N et al. Pharmacokinetics of high-dose oseltamivir in healthy volunteers. Antimicrob Agents Chemother 2009; 53:945-952.
22. Cass LM, Efthymiopoulos C, Bye A. Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin Pharmacokinet 1999; 36(Suppl 1):1-11.
23. Peng AW, Milleri S, Stein DS. Direct measurement of the anti-influenza agent zanamivir in the respiratory tract following inhalation. Antimicrob Agents Chemother 2000; 44:1974-1976.
24. Gubareva LV, Kaiser L, Matrosovich MN, Soo-Hoo Y, Hayden FG. Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis 2001; 183:523-531.
25. Ives J, Carr J, Roberts NA et al. An oseltamivir treatment-selected influenza A:N2 virus with a R292K mutation in the neuraminidase gene has reduced infectivity in vivo. J Clinical Virol 2000; 18:251-269.
26. Jackson HC, Roberts N, Wange ZM, Belshe R. Management of influenza. Use of new antivirals and resistance in perspective. Clin Drug Invest 2000; 20:447-454.
27. Gubareva LV, Matrosovich MN, Brenner MK, Bethell RC, Webster RG. Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. J Infect Dis 1998; 178:1257-1262.
28. Whitley RJ, Hayden FG, Reisinger KS et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001; 20:127-133.
29. Ward P, Small I, Smith J, Suter P, Dutkowski R. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother 2005; 55(Suppl 1):i5-i21.
30. Kiso M, Mitamura K, Sakai-Tagawa Y et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 2004; 364:759-765.
31. Earhart KC, Elsayed NM, Saad MD et al. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt. J Infect Public Health 2009; 2:74-80.
32. Le QM, Kiso M, Someya K et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature 2005; 437:1108.
33. Stephenson I, Democratis J, Lackenby A et al. Neuraminidase Inhibitor Resistance after Oseltamivir Treatment of Acute Influenza A and B in Children. Clin Infect Dis 2009; 48:289-296.
34. Yates PJ, Mehta N, Tisdale M. Resistance analysis of a Phase IV clinical trial of zanamivir treatment in children infected with influenza. Options for the Control of Influenza VII; 3-7 September 2010; Hong Kong, SAR China. 139-159.
35. Herlocher ML, Truscon R, Elias S et al. Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 2004; 190:1627-1630.
36. Herlocher ML, Carr J, Ives J et al. Influenza virus carrying an R292K mutation in the neuraminidase gene is not transmitted in ferrets. Antiviral Res 2002; 54:99-111.
37. Dharan NJ, Gubareva LV, Meyer JJ et al. Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA 2009; 301:1034-1041.
38. Matsuzaki Y, Mizuta K, Aoki Y et al. A two-year survey of the oseltamivir-resistant influenza A(H1N1) virus in Yamagata, Japan and the clinical effectiveness of oseltamivir and zanamivir. Virol J 2010; 7:53.
39. Meijer A, Lackenby A, Hungnes O et al. Oseltamivir-resistant influenza virus A (H1N1), Europe, 2007-08 season. Emerg Infect Dis 2009; 15:552-560.
40. Hurt AC, Ernest J, Deng YM et al. Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa. Antiviral Res 2009; 83:90-93.
41. Bloom JD, Gong LI, Baltimore D. Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science 2010; 328:1272-1275.
42. Abed Y, Pizzorno A, Bouhy X, Boivin G. Role of Permissive Neuraminidase Mutations in Influenza A/Brisbane/59/2007-like (H1N1) Viruses. PLoS Pathog 2011; 7:e1002431.
43. Rameix-Welti MA, Munier S, Le Gal S et al. Neuraminidase of 2007-2008 influenza A(H1N1) viruses shows increased affinity for sialic acids due to the D344N substitution. Antivir Ther 2011; 16:597-603.
44. Collins PJ, Haire LF, Lin YP et al. Structural basis for oseltamivir resistance of influenza viruses. Vaccine 2009; 27:6317-6323.
45. Monto AS, McKimm-Breschkin JL, Macken C et al. Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3years of their use. Antimicrob Agents Chemother 2006; 50:2395-2402.
46. Inoue M, Barkham T, Leo YS et al. Emergence of oseltamivir-resistant pandemic (H1N1) 2009 virus within 48hours. Emerg Infect Dis 2010; 16:1633-1636.
47. Valinotto LE, Diez RA, Barrero PR et al. Emergence of intratreatment resistance to oseltamivir in pandemic influenza A H1N1 2009 virus. Antivir Ther 2010; 15:923-927.
48. Renaud C, Pergam SA, Polyak C et al. Early emergence of an H275Y mutation in a hematopoietic cell transplant recipient treated with intravenous peramivir. Transpl Infect Dis 2010; 12:513-517.
49. CDC. Oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in two summer campers receiving prophylaxis--North Carolina, 2009. MMWR Morb Mortal Wkly Rep 2009; 58:969-972.
50. Baz M, Abed Y, Papenburg J et al. Emergence of oseltamivir-resistant pandemic H1N1 virus during prophylaxis. N Engl J Med 2009; 361:2296-2297.
51. Harvala H, Gunson R, Simmonds P et al. The emergence of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus amongst hospitalised immunocompromised patients in Scotland, November-December, 2009. Euro Surveill 2010; 15:pii:19536.
52. Tramontana AR, George B, Hurt AC et al. Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. Emerg Infect Dis 2010; 16:1068-1075.
53. Campanini G, Piralla A, Rovida F et al. First case in Italy of acquired resistance to oseltamivir in an immunocompromised patient with influenza A/H1N1v infection. J Clin Virol 2010; 48:220-222.
54. Memoli MJ, Hrabal RJ, Hassantoufighi A, Eichelberger MC, Taubenberger JK. Rapid selection of oseltamivir- and peramivir-resistant pandemic H1N1 virus during therapy in 2 immunocompromised hosts. Clin Infect Dis 2010; 50:1252-1255.
55. Chan PA, Connell NT, Gabonay AM et al. Oseltamivir-resistant 2009-2010 pandemic influenza A (H1N1) in an immunocompromised patient. Clin Microbiol Infect 2010; 16:1576-1578.
56. Chen LF, Dailey NJ, Rao AK et al. Cluster of oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infections on a hospital ward among immunocompromised patients--North Carolina, 2009. J Infect Dis 2011; 203:838-846.
57. Moore C, Galiano M, Lackenby A et al. Evidence of person-to-person transmission of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus in a hematology unit. J Infect Dis 2011; 203:18-24.
58. Chen H, Cheung CL, Tai H et al. Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China. Emerg Infect Dis 2009; 15:1970-1972.
59. Le QM, Wertheim HF, Tran ND et al. A community cluster of oseltamivir-resistant cases of 2009 H1N1 influenza. N Engl J Med 2010; 362:86-87.
60. Hurt AC, Hardie K, Wilson NJ et al. Community Transmission of Oseltamivir-Resistant A(H1N1)pdm09 Influenza. N Engl J Med 2011; 365:2541-2542.
61. Hamelin ME, Baz M, Abed Y et al. Oseltamivir-resistant pandemic A/H1N1 virus is as virulent as its wild-type counterpart in mice and ferrets. PLoS Pathog 2010; 6:e1001015.
62. Seibert CW, Kaminski M, Philipp J et al. Oseltamivir-resistant variants of the 2009 pandemic H1N1 influenza A virus are not attenuated in the guinea pig and ferret transmission models. J Virol 2010; 84:11219-11226.
63. Brookes DW, Miah S, Lackenby A, Hartgroves L, Barclay WS. Pandemic H1N1 2009 influenza virus with the H275Y oseltamivir resistance neuraminidase mutation shows a small compromise in enzyme activity and viral fitness. J Antimicrob Chemother 2011; 66:466-470.
64. Duan S, Boltz DA, Seiler P et al. Oseltamivir-resistant pandemic H1N1/2009 influenza virus possesses lower transmissibility and fitness in ferrets. PLoS Pathog 2010; 6:e1001022.
65. Nguyen HT, Fry AM, Loveless PA, Klimov AI, Gubareva LV. Recovery of a multidrug-resistant strain of pandemic influenza A 2009 (H1N1) virus carrying a dual H275Y/I223R mutation from a child after prolonged treatment with oseltamivir. Clin Infect Dis 2010; 51:983-984.
66. Van der Vries E, Stelma FF, Boucher CA. Emergence of a multidrug-resistant pandemic influenza A (H1N1) virus. N Engl J Med 2010; 363:1381-1382.
67. Eshaghi A, Patel SN, Sarabia A et al. Multidrug-resistant pandemic (H1N1) 2009 infection in immunocompetent child. Emerg Infect Dis 2011; 17:1472-1474.
68. WHO. Update on oseltamivir resistance in influenza A(H1N1)2009 viruses, number 144. 2011 Available at http://www.who.int/influenza/surveillance_monitoring/updates/2011_10_07_weekly_web_update_oseltamivir_resistance.pdf (Accessed 12 October 2011).
69. CDC. 2009-2010 Influenza Season Summary. 2010 Available at http://www.cdc.gov/flu/weekly/weeklyarchives2009-2010/09-10summary.htm (Accessed 15 October 2011).
70. Lackenby A, Moran Gilad J, Pebody R et al. Continued emergence and changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus, United Kingdom, winter 2010/11. Euro Surveill 2011; 16:pii=19784.
71. Storms AD, Gubareva LV, Su S et al. Oseltamivir-resistant pandemic (H1N1) 2009 virus infections, United States, 2010-11. Emerg Infect Dis 2012; 18:308-311.
72. CDC. Updated CDC Estimates of 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, April 2009-April 10. 2010 Available at http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm (Accessed 20 May 2010).
73. Zurcher T, Yates PJ, Daly J et al. Mutations conferring zanamivir resistance in human influenza virus N2 neuraminidases compromise virus fitness and are not stably maintained in vitro. J Antimicrob Chemother 2006; 58:723-732.
74. Abed Y, Baz M, Boivin G. Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the N1 and N2 genetic backgrounds. Antivir Ther 2006; 11:971-976.
75. Okomo-Adhiambo M, Demmler-Harrison GJ, Deyde VM et al. Detection of E119V and E119I mutations in influenza A (H3N2) viruses isolated from an immunocompromised patient: challenges in diagnosis of oseltamivir resistance. Antimicrob Agents Chemother 2010; 54:1834-1841.
76. McKimm-Breschkin JL, Sahasrabudhe A, Blick TJ et al. Mutations in a conserved residue in the influenza virus neuraminidase active site decreases sensitivity to Neu5Ac2en-derived inhibitors. J Virol 1998; 72:2456-2462.
77. Smith BJ, McKimm-Breschkin JL, McDonald M et al. Structural studies of the resistance of influenza virus neuramindase to inhibitors. J Med Chem 2002; 45:2207-2212.
78. Gubareva LV. Molecular mechanisms of influenza virus resistance to neuraminidase inhibitors. Virus Res 2004; 103:199-203.
79. Baz M, Abed Y, McDonald J, Boivin G. Characterization of multidrug-resistant influenza A/H3N2 viruses shed during 1year by an immunocompromised child. Clin Infect Dis 2006; 43:1555-1561.
80. Simon P, Holder BP, Bouhy X et al. The I222V neuraminidase mutation has a compensatory role in replication of an oseltamivir-resistant influenza virus A/H3N2 E119V mutant. J Clin Microbiol 2011; 49:715-717.
81. Dapat C, Suzuki Y, Saito R et al. Rare influenza A (H3N2) variants with reduced sensitivity to antiviral drugs. Emerg Infect Dis 2010; 16:493-496.
82. Sugaya N, Mitamura K, Yamazaki M et al. Lower clinical effectiveness of oseltamivir against influenza B contrasted with influenza A infection in children. Clin Infect Dis 2007; 44:197-202.
83. Hatakeyama S, Sugaya N, Ito M et al. Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. JAMA 2007; 297:1435-1442.
84. Hurt AC, Iannello P, Jachno K et al. Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient. Antimicrob Agents Chemother 2006; 50:1872-1874.
85. Sleeman K, Sheu TG, Moore Z et al. Influenza B viruses with mutation in the neuraminidase active site, North Carolina, USA, 2010-11. Emerg Infect Dis 2011; 17:2043-2046.
86. Moscona A, McKimm-Breschkin J. News about influenza B drug resistance that cannot be ignored. JAMA 2007; 297:1492-1493.
87. De Jong MD, Tran TT, Truong HK et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005; 353:2667-2672.
88. Hill AW, Guralnick RP, Wilson MJC, Habib F, Janies D. Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza. Infect Genet Evol 2009; 9:169-178.
89. McKimm-Breschkin JL, Selleck P, Usman TB, Johnson MA. Reduced Sensitivity of influenza A (H5N1) to Oseltamivir. Emerg Infect Dis 2007; 13:1354-1357.
90. Collins PJ, Haire LF, Lin YP et al. Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants. Nature 2008; 453:1258-1261.
91. Ilyushina NA, Seiler JP, Rehg JE, Webster RG, Govorkova EA. Effect of neuraminidase inhibitor-resistant mutations on pathogenicity of clade 2.2 A/Turkey/15/06 (H5N1) influenza virus in ferrets. PLoS Pathog 2010; 6:e1000933.
92. Ilyushina NA, Hay A, Yilmaz N et al. Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice. Antimicrob Agents Chemother 2008; 52:3889-3897.
93. Yen H-L, Lipatov AS, Ilyushina NA et al. Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model. J Virol 2007; 81:6890-6898.
94. Hurt AC, Holien JK, Barr IG. In vitro generation of neuraminidase inhibitor resistance in A(H5N1) influenza viruses. Antimicrob Agents Chemother 2009; 53:4433-4440.
95. McKimm-Breschkin J, Barrett S, Pudjiatmoko P et al. Screening neuraminidase inhibitor susceptibility of avian influenza isolates from SE Asia 2005-2009 identifies H5N1 I222 mutants with reduced oseltamivir sensitivity. XIV International Symposium on Respiratory Virus Infections; 23-26 March; Istanbul, Turkey: The Macrae Foundation; p3.
96. Boltz DA, Douangngeun B, Phommachanh P et al. Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People's Democratic Republic. J Gen Virol 2010; 91:949-959.
97. Varghese JN, Smith PW, Sollis SL et al. Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase. Structure 1998; 6:735-746.
98. Russell RJ, Haire LF, Stevens DJ et al. The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 2006; 443:45-49.
99. Hatakeyama S, Ozawa M, Kawaoka Y. In vitro selection of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. Clin Microbiol Infect 2011; 17:1332-1335.
100. Gubareva LV, Robinson MJ, Bethell RC, Webster RG. Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en. J Virol 1997; 71:3385-3390.
101. Blick TJ, Tiong T, Sahasrabudhe A et al. Generation and characterization of an influenza virus neuraminidase variant with decreased sensitivity to the neuraminidase-specific inhibitor 4-guanidino-Neu5Ac2en. Virology 1995; 214:475-484.
102. Colacino JM, Chirgadze NY, Garman E et al. A single sequence change destabilizes the influenza virus neuraminidase tetramer. Virology 1997; 236:66-75.
103. McKimm-Breschkin JL, McDonald M, Blick TJ, Colman PM. Mutation in the influenza virus neuraminidase gene resulting in decreased sensitivity to the neuraminidase inhibitor 4-guanidino- Neu5Ac2en leads to instability of the enzyme. Virology 1996; 225:240-242.
104. Sahasrabudhe A, Lawrence L, Epa VC et al. Substrate, inhibitor, or antibody stabilizes the Glu 119 Gly mutant influenza virus neuraminidase. Virology 1998; 247:14-21.
105. Ison MG, Gubareva LV, Atmar RL, Treanor J, Hayden FG. Recovery of drug-resistant influenza virus from immunocompromised patients: a case series. J Infect Dis 2006; 193:760-764.
106. Sheu TG, Deyde VM, Okomo-Adhiambo M et al. Surveillance for Neuraminidase Inhibitor Resistance among Human Influenza A and B Viruses Circulating Worldwide from 2004 to 2008. Antimicrob Agents Chemother 2008; 52:3284-3292.
107. Oakley AJ, Barrett S, Peat TS et al. Structural and functional basis of resistance to neuraminidase inhibitors of influenza B viruses. J Med Chem 2010; 53:6421-6431.
108. Baum EZ, Wagaman PC, Ly L et al. A point mutation in influenza B neuraminidase confers resistance to peramivir and loss of slow binding. Antiviral Res 2003; 59:13-22.
109. Hart GJ, Bethell RC. 2, 3-didehydro-2, 4-dideoxy-4-guanidino-N-acetyl-D-neuraminic acid (4-guanidino-Neu5Ac2en) is a slow-binding inhibitor of sialidase from both influenza A virus and influenza B virus. Biochem Mol Biol Int 1995; 36:695-703.
110. Kati WM, Saldivar AS, Mohamadi F et al. GS4071 is a slow-binding inhibitor of influenza neuraminidase from both A and B strains. Biochem Biophys Res Commun 1998; 244:408-413.
111. Pegg MS, Von Itzstein M. Slow-binding inhibition of sialidase from influenza virus. Biochem Mol Biol Int 1994; 32:851-858.
112. Barrett S, Mohr PG, Schmidt PM, McKimm-Breschkin JL. Real time enzyme inhibition assays provide insights into differences in binding of neuraminidase inhibitors to wild type and mutant influenza viruses. PLoS ONE 2011; 6:e23627.
113. McKimm-Breschkin J, Williams J, Attwood RM et al. A Y155H mutation in a non-conserved residue in the influenza neuraminidase confers resistance to all neuraminidase inhibitors. Influenza Antivirals: Efficacy and Resistance; 8-10 November; Rio de Janeiro, Brazil: ISIRV Antiviral Group; pO33, p66.
114. Barrett S, Mohr P, McKimm-Breschkin J. A solid phase reactivation assay demonstrates differences in dissociation of the neuraminidase inhibitors from wild type and mutant viruses. Influenza Antivirals: Efficacy and Resistance; 8-10 November; Rio de Janeiro, Brazil: ISIRV Antiviral Group; p84, P19.
115. Nguyen HT, Fry AM, Gubareva LV. Neuraminidase inhibitor resistance in influenza viruses and laboratory testing methods. Antivir Ther 2012; 17:159-173.