Swine Influenza pp 273-300

Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 370) | Cite as

Therapeutics Against Influenza

Chapter

Abstract

Despite 75 years of research into prevention and treatment of influenza, the viruses that cause this disease continue to rank as some of the most important pathogens afflicting humans today. Progress in development of therapeutics for influenza has been slow for much of that time, but has accelerated in pace over the last two decades. Two classes of antiviral medications are used in humans at present, but each has limitations in scope and effectiveness of use. New strategies involving these licensed agents, including alternate forms of delivery and combination therapy with other drugs, are currently being explored. In addition, several novel antiviral compounds are in various clinical phases of development. Together with strategies designed to target the virus itself, new approaches to interrupt host–pathogen interactions or modulate detrimental aspects of the immune response have been proposed. Therapy for influenza will likely undergo substantial changes in the decades to come, evolving with our knowledge of pathogenesis as new approaches become viable and are validated clinically.

References

  1. Aldridge JR Jr, Moseley CE, Boltz DA et al (2009) TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci USA 106:5306–5311PubMedCrossRefGoogle Scholar
  2. Alvarez R, Elbashir S, Borland T et al (2009) RNA interference-mediated silencing of the respiratory syncytial virus nucleocapsid defines a potent antiviral strategy. Antimicrob Agents Chemother 53:3952–3962PubMedCrossRefGoogle Scholar
  3. Aoki FY, Macleod MD, Paggiaro P et al (2003) Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 51:123–129PubMedCrossRefGoogle Scholar
  4. Aoki FY, Sitar DS (1988) Clinical pharmacokinetics of amantadine hydrochloride. Clin Pharmacokinet 14:35–51PubMedCrossRefGoogle Scholar
  5. Appleyard G (1977) Amantadine-resistance as a genetic marker for influenza viruses. J Gen Virol 36:249–255PubMedCrossRefGoogle Scholar
  6. Babu YS, Chand P, Bantia S et al (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 43:3482–3486PubMedCrossRefGoogle Scholar
  7. Barr IG, Hurt AC, Iannello P et al (2007) Increased adamantane resistance in influenza A(H3) viruses in Australia and neighbouring countries in 2005. Antiviral Res 73:112–117PubMedCrossRefGoogle Scholar
  8. Barr IG, Deng YM, Iannello P et al (2008) Adamantane resistance in influenza A(H1) viruses increased in 2007 in South East Asia but decreased in Australia and some other countries. Antiviral Res 80:200–205PubMedCrossRefGoogle Scholar
  9. Barrientos LG, O’Keefe BR, Bray M et al (2003) Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res 58:47–56PubMedCrossRefGoogle Scholar
  10. Baz M, Abed Y, Papenburg J et al (2009) Emergence of oseltamivir-resistant pandemic H1N1 virus during prophylaxis. N Engl J Med 361:2296–2297PubMedCrossRefGoogle Scholar
  11. bdel-Ghafar AN, Chotpitayasunondh T, Gao Z et al (2008) Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 358:261–273CrossRefGoogle Scholar
  12. Bearman GM, Shankaran S, Elam K (2010) Treatment of severe cases of pandemic (H1N1) 2009 influenza: review of antivirals and adjuvant therapy. Recent Pat Antiinfect Drug Discov 5:152–156PubMedGoogle Scholar
  13. Beigel JH, Farrar J, Han AM et al (2005) Avian influenza A (H5N1) infection in humans. N Engl J Med 353:1374–1385PubMedCrossRefGoogle Scholar
  14. Belser JA, Lu X, Szretter KJ et al (2007) DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection. J Infect Dis 196:1493–1499PubMedCrossRefGoogle Scholar
  15. Belshe RB, Smith MH, Hall CB et al (1988) Genetic basis of resistance to rimantadine emerging during treatment of influenza virus infection. J Virol 62:1508–1512PubMedGoogle Scholar
  16. Betakova T, Ciampor F, Hay AJ (2005) Influence of residue 44 on the activity of the M2 proton channel of influenza A virus. J Gen Virol 86:181–184PubMedCrossRefGoogle Scholar
  17. Birnkrant D, Cox E (2009) The emergency use authorization of peramivir for treatment of 2009 H1N1 influenza. N Engl J Med 361:2204–2207PubMedCrossRefGoogle Scholar
  18. Boyd MR, Gustafson KR, McMahon JB et al (1997) Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrob Agents Chemother 41:1521–1530PubMedGoogle Scholar
  19. Bright RA, Medina MJ, Xu X et al (2005) Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 366:1175–1181PubMedCrossRefGoogle Scholar
  20. Bright RA, Shay DK, Shu B et al (2006) Adamantane resistance among influenza A viruses isolated early during the 2005–2006 influenza season in the United States. JAMA 295:891–894PubMedCrossRefGoogle Scholar
  21. Budd A, Alleva L, Alsharifi M et al (2007) Increased survival after gemfibrozil treatment of severe mouse influenza. Antimicrob Agents Chemother 51:2965–2968PubMedCrossRefGoogle Scholar
  22. Calfee DP, Peng AW, Cass LM et al (1999) Safety and efficacy of intravenous zanamivir in preventing experimental human influenza A virus infection. Antimicrob Agents Chemother 43:1616–1620PubMedGoogle Scholar
  23. Carr J, Ives J, Kelly L et al (2002) Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo. Antiviral Res 54:79–88PubMedCrossRefGoogle Scholar
  24. Cass LM, Efthymiopoulos C, Bye A (1999) Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin Pharmacokinet 36(Suppl 1):1–11PubMedCrossRefGoogle Scholar
  25. Centers for Disease Control (2006) High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents—United States, 2005–06 influenza season. MMWR Morb Mortal Wkly Rep 55:44–46Google Scholar
  26. Centers for Disease Control (2009) Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients—Seattle, Washington, 2009. MMWR Morb Mortal Wkly Rep 58:893–896Google Scholar
  27. Centers for Disease Control (2010) Update: influenza activity—United States, August 30, 2009–March 27, 2010, and composition of the 2010–11 influenza vaccine. MMWR Morb Mortal Wkly Rep 59:423–430Google Scholar
  28. Clinical Trials.gov (2010). http://www.ClinicalTrials.gov. Accessed 8/4/10
  29. Colman PM (1994) Influenza virus neuraminidase: structure, antibodies, and inhibitors. Protein Sci 3:1687–1696PubMedCrossRefGoogle Scholar
  30. Colman PM, Hoyne PA, Lawrence MC (1993) Sequence and structure alignment of paramyxovirus hemagglutinin-neuraminidase with influenza virus neuraminidase. J Virol 67:2972–2980PubMedGoogle Scholar
  31. Dapat C, Suzuki Y, Saito R et al (2010) Rare influenza A (H3N2) variants with reduced sensitivity to antiviral drugs. Emerg Infect Dis 16:493–496PubMedCrossRefGoogle Scholar
  32. Davies WL, Grunert RR, Haff RF et al (1964) Antiviral activity of 1-adamantanamine (amantadine). Science 144:862–863PubMedCrossRefGoogle Scholar
  33. De Clerq E (2006) Antiviral agents active against influenza A viruses. Nat Rev Drug Discov 5:1015–1025CrossRefGoogle Scholar
  34. DeVincenzo J, Lambkin-Williams R, Wilkinson T et al (2010) A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci USA 107:8800–8805PubMedCrossRefGoogle Scholar
  35. Deyde V, Garten R, Sheu T et al (2009) Genomic events underlying the changes in adamantane resistance among influenza A(H3N2) viruses during 2006–2008. Influenza Other Respi Viruses 3:297–314PubMedCrossRefGoogle Scholar
  36. Deyde VM, Xu X, Bright RA et al (2007) Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. J Infect Dis 196:249–257PubMedCrossRefGoogle Scholar
  37. Dharan NJ, Gubareva LV, Meyer JJ et al (2009) Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States. JAMA 301:1034–1041PubMedCrossRefGoogle Scholar
  38. Dolin R, Reichman RC, Madore HP et al (1982) A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. N Engl J Med 307:580–584PubMedCrossRefGoogle Scholar
  39. Doyle WJ, Skoner DP, Alper CM et al (1998) Effect of rimantadine treatment on clinical manifestations and otologic complications in adults experimentally infected with influenza A (H1N1) virus. J Infect Dis 177:1260–1265PubMedCrossRefGoogle Scholar
  40. Duan S, Boltz DA, Seiler P et al (2010) Oseltamivir-resistant pandemic H1N1/2009 influenza virus possesses lower transmissibility and fitness in ferrets. PLoS Pathog 6:e1001022PubMedCrossRefGoogle Scholar
  41. Dutkowski R, Smith JR, Davies BE (2010) Safety and pharmacokinetics of oseltamivir at standard and high dosages. Int J Antimicrob Agents 35:461–467PubMedCrossRefGoogle Scholar
  42. Endo Pharmaceuticals Inc (2007) Amantadine Package Insert. http://www.endo.com/PDF/symmetrel_pack_insert.pdf
  43. Falagas ME, Vouloumanou EK, Baskouta E et al (2010) Treatment options for 2009 H1N1 influenza: evaluation of the published evidence. Int J Antimicrob Agents 35:421–430PubMedCrossRefGoogle Scholar
  44. Fedson DS (2008) Confronting an imminent pandemic with inexpensive generic agents: can it be done? Lancet Infect Dis 8:571–576PubMedCrossRefGoogle Scholar
  45. Fedson DS (2009) Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents: why they are needed and how they might work. Influenza Other Respi Viruses 3:129–142PubMedCrossRefGoogle Scholar
  46. Ferraris O, Lina B (2008) Mutations of neuraminidase implicated in neuraminidase inhibitors resistance. J Clin Virol 41:13–19PubMedCrossRefGoogle Scholar
  47. Fleming DM, Verlander NQ, Elliot AJ et al (2010) An assessment of the effect of statin use on the incidence of acute respiratory infections in England during winters 1998–1999 to 2005–2006. Epidemiol Infect 138:1281–1288 PubMedCrossRefGoogle Scholar
  48. Forest Pharmaceuticals Inc (2010) Rimantadine Package Insert. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019649s015lbl.pdf
  49. Furuta Y, Takahashi K, Fukuda Y et al (2002) In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother 46:977–981PubMedCrossRefGoogle Scholar
  50. Furuta Y, Takahashi K, Kuno-Maekawa M et al (2005) Mechanism of action of T-705 against influenza virus. Antimicrob Agents Chemother 49:981–986PubMedCrossRefGoogle Scholar
  51. Furuta Y, Takahashi K, Shiraki K et al (2009) T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res 82:95–102PubMedCrossRefGoogle Scholar
  52. Galabov AS, Simeonova L, Gegova G (2006) Rimantadine and oseltamivir demonstrate synergistic combination effect in an experimental infection with type A (H3N2) influenza virus in mice. Antivir Chem Chemother 17:251–258PubMedGoogle Scholar
  53. Geiler J, Michaelis M, Naczk P et al (2010) N-acetyl-l-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochem Pharmacol 79:413–420PubMedCrossRefGoogle Scholar
  54. Gething MJ, Doms RW, York D et al (1986) Studies on the mechanism of membrane fusion: site-specific mutagenesis of the hemagglutinin of influenza virus. J Cell Biol 102:11–23PubMedCrossRefGoogle Scholar
  55. Govorkova EA, Fang HB, Tan M et al (2004) Neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in MDCK cells. Antimicrob Agents Chemother 48:4855–4863PubMedCrossRefGoogle Scholar
  56. Govorkova EA, Webster RG (2010) Combination chemotherapy for influenza. Viruses 2:1510–1529CrossRefGoogle Scholar
  57. Grambas S, Bennett MS, Hay AJ (1992) Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses. Virology 191:541–549PubMedCrossRefGoogle Scholar
  58. Gubareva LV, Robinson MJ, Bethell RC et al (1997) Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en. J Virol 71:3385–3390PubMedGoogle Scholar
  59. Gubareva LV, Kaiser L, Hayden FG (2000) Influenza virus neuraminidase inhibitors. Lancet 355:827–835PubMedCrossRefGoogle Scholar
  60. Gulland A (2009) First cases of spread of oseltamivir resistant swine flu between patients are reported in Wales. BMJ 339:b4975PubMedCrossRefGoogle Scholar
  61. Gums JG, Pelletier EM, Blumentals WA (2008) Oseltamivir and influenza-related complications, hospitalization and healthcare expenditure in healthy adults and children. Expert Opin Pharmacother 9:151–161PubMedCrossRefGoogle Scholar
  62. Harper SA, Bradley JS, Englund JA et al (2009) Seasonal influenza in adults and children–diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 48:1003–1032PubMedCrossRefGoogle Scholar
  63. Harter G, Zimmermann O, Maier L et al (2010) Intravenous zanamivir for patients with pneumonitis due to pandemic (H1N1) 2009 influenza virus. Clin Infect Dis 50:1249–1251PubMedCrossRefGoogle Scholar
  64. Hay AJ, Zambon MC, Wolstenholme AJ et al (1986) Molecular basis of resistance of influenza A viruses to amantadine. J Antimicrob Chemother 18(Suppl B):19–29Google Scholar
  65. Hayden FG, Schlepushkin AN, Pushkarskaya NL (1984) Combined interferon-alpha 2, rimantadine hydrochloride, and ribavirin inhibition of influenza virus replication in vitro. Antimicrob Agents Chemother 25:53–57PubMedCrossRefGoogle Scholar
  66. Hayden FG, Monto AS (1986) Oral rimantadine hydrochloride therapy of influenza A virus H3N2 subtype infection in adults. Antimicrob Agents Chemother 29:339–341PubMedCrossRefGoogle Scholar
  67. Hayden FG (1996) Amantidine and rimantidine-clinical aspects. In: Richman DD (ed) Antiviral Drug Resistance, Wiley, pp. 59–77Google Scholar
  68. Hayden FG, Osterhaus AD, Treanor JJ et al (1997) Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group. N Engl J Med 337:874–880PubMedCrossRefGoogle Scholar
  69. Hayden FG, Atmar RL, Schilling M et al (1999a) Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med 341:1336–1343PubMedCrossRefGoogle Scholar
  70. Hayden FG, Treanor JJ, Fritz RS et al (1999b) Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA 282:1240–1246PubMedCrossRefGoogle Scholar
  71. Hayden FG, Gubareva LV, Monto AS et al (2000) Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group. N Engl J Med 343:1282–1289PubMedCrossRefGoogle Scholar
  72. Hayden FG, Belshe R, Villanueva C et al (2004) Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. J Infect Dis 189:440–449PubMedCrossRefGoogle Scholar
  73. Hayden FG (2006) Antiviral resistance in influenza viruses—implications for management and pandemic response. N Engl J Med 354:785–788PubMedCrossRefGoogle Scholar
  74. Hayden F (2009) Developing new antiviral agents for influenza treatment: what does the future hold? Clin Infect Dis 48(Suppl 1):S3–S13PubMedCrossRefGoogle Scholar
  75. He G, Massarella J, Ward P (1999) Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64–0802. Clin Pharmacokinet 37:471–484PubMedCrossRefGoogle Scholar
  76. Herlocher ML, Carr J, Ives J et al (2002) Influenza virus carrying an R292K mutation in the neuraminidase gene is not transmitted in ferrets. Antiviral Res 54:99–111PubMedCrossRefGoogle Scholar
  77. Herlocher ML, Truscon R, Elias S et al (2004) Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 190:1627–1630PubMedCrossRefGoogle Scholar
  78. Honda T, Kubo S, Masuda T et al (2009) Synthesis and in vivo influenza virus-inhibitory effect of ester prodrug of 4-guanidino-7-O-methyl-Neu5Ac2en. Bioorg Med Chem Lett 19:2938–2940PubMedCrossRefGoogle Scholar
  79. Hu J, Doucette K, Hartling L et al (2010) Treatment of hepatitis C in children: a systematic review. PLoS ONE 5:e11542PubMedCrossRefGoogle Scholar
  80. Hurt AC, Holien JK, Parker M et al (2009) Zanamivir-resistant influenza viruses with a novel neuraminidase mutation. J Virol 83:10366–10373PubMedCrossRefGoogle Scholar
  81. Ilyushina NA, Hoffmann E, Salomon R et al (2007) Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice. Antivir Ther 12:363–370PubMedGoogle Scholar
  82. Ilyushina NA, Hay A, Yilmaz N et al (2008) Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice. Antimicrob Agents Chemother 52:3889–3897PubMedCrossRefGoogle Scholar
  83. Ishizuka H, Yoshiba S, Okabe H et al (2010) Clinical pharmacokinetics of Laninamivir, a novel long-acting neuraminidase inhibitor, after single and multiple inhaled doses of Its prodrug, CS-8958, in Healthy Male Volunteers. J Clin Pharmacol 50:1319–1329 PubMedCrossRefGoogle Scholar
  84. Ison MG, Gnann JW Jr, Nagy-Agren S et al (2003) Safety and efficacy of nebulized zanamivir in hospitalized patients with serious influenza. Antivir Ther 8:183–190PubMedGoogle Scholar
  85. Itoh Y, Shinya K, Kiso M et al (2009) In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460:1021–1025PubMedGoogle Scholar
  86. Ives JA, Carr JA, Mendel DB et al (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 55:307–317PubMedCrossRefGoogle Scholar
  87. Jefferson T, Jones M, Doshi P et al (2010) Neuraminidase inhibitors for preventing and treating influenza in healthy adults. Cochrane Database Syst Rev 2:CD001265Google Scholar
  88. Kaiser L, Wat C, Mills T et al (2003) Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 163:1667–1672PubMedCrossRefGoogle Scholar
  89. Kashyap AK, Steel J, Rubrum A et al (2010) Protection from the 2009 H1N1 pandemic influenza by an antibody from combinatorial survivor-based libraries. PLoS Pathog 6:e1000990PubMedCrossRefGoogle Scholar
  90. Kawai N, Ikematsu H, Iwaki N et al (2008) A comparison of the effectiveness of zanamivir and oseltamivir for the treatment of influenza A and B. J Infect 56:51–57PubMedCrossRefGoogle Scholar
  91. Kim CU, Lew W, Williams MA et al (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 119:681–690PubMedCrossRefGoogle Scholar
  92. Kimberlin DW, Shalabi M, Abzug MJ et al (2010) Safety of oseltamivir compared with the adamantanes in children less than 12 months of age. Pediatr Infect Dis J 29:195–198PubMedCrossRefGoogle Scholar
  93. Kiso M, Mitamura K, Sakai-Tagawa Y et al (2004) Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 364:759–765PubMedCrossRefGoogle Scholar
  94. Kiso M, Kubo S, Ozawa M et al (2010a) Efficacy of the new neuraminidase inhibitor CS-8958 against H5N1 influenza viruses. PLoS Pathog 6:e1000786PubMedCrossRefGoogle Scholar
  95. Kiso M, Takahashi K, Sakai-Tagawa Y et al (2010b) T-705 (favipiravir) activity against lethal H5N1 influenza A viruses. Proc Natl Acad Sci USA 107:882–887PubMedCrossRefGoogle Scholar
  96. Kong LK, Zhou BP (2006) Successful treatment of avian influenza with convalescent plasma. Hong Kong Med J 12:489PubMedGoogle Scholar
  97. Koyama K, Takahashi M, Oitate M et al (2009) CS-8958, a prodrug of the novel neuraminidase inhibitor R-125489, demonstrates a favorable long-retention profile in the mouse respiratory tract. Antimicrob Agents Chemother 53:4845–4851PubMedCrossRefGoogle Scholar
  98. Krause JC, Tumpey TM, Huffman CJ et al (2010) Naturally occurring human monoclonal antibodies neutralize both 1918 and 2009 pandemic influenza A (H1N1) viruses. J Virol 84:3127–3130PubMedCrossRefGoogle Scholar
  99. Kubo S, Tomozawa T, Kakuta M et al (2010) Laninamivir prodrug CS-8958, a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration. Antimicrob Agents Chemother 54:1256–1264PubMedCrossRefGoogle Scholar
  100. Kumar A, Zarychanski R, Pinto R et al (2009) Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 302:1872–1879PubMedCrossRefGoogle Scholar
  101. Kumar P, Sood V, Vyas R et al (2010) Potent inhibition of influenza virus replication with novel siRNA-chimeric-ribozyme constructs. Antiviral Res 87:204–212PubMedCrossRefGoogle Scholar
  102. Kuritzkes DR, Walker BD (2007) HIV-1: pathogenesis, clinical manifestations, and treatment. In: Knipe DM, Howley PM (eds) Fields virology, Fifth, 5th edn. Lippincott Williams and Wilkins, Philadelphia, pp 1697–1701Google Scholar
  103. Kwong JC, Li P, Redelmeier DA (2009) Influenza morbidity and mortality in elderly patients receiving statins: a cohort study. PLoS ONE 4:e8087PubMedCrossRefGoogle Scholar
  104. Lackenby A, Hungnes O, Dudman SG et al (2008) Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe. Euro Surveill 13:8026 Google Scholar
  105. Le QM, Kiso M, Someya K et al (2005) Avian flu: isolation of drug-resistant H5N1 virus. Nature 437:1108PubMedCrossRefGoogle Scholar
  106. Le QM, Wertheim HF, Tran ND et al (2010) A community cluster of oseltamivir-resistant cases of 2009 H1N1 influenza. N Engl J Med 362:86–87PubMedGoogle Scholar
  107. Leneva IA, Roberts N, Govorkova EA et al (2000) The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res 48:101–115PubMedCrossRefGoogle Scholar
  108. Leung TW, Tai AL, Cheng PK et al (2009) Detection of an oseltamivir-resistant pandemic influenza A/H1N1 virus in Hong Kong. J Clin Virol 46:298–299PubMedCrossRefGoogle Scholar
  109. Liu Z, Guo Z, Wang G et al (2009) Evaluation of the efficacy and safety of a statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in BALB/c mice. Eur J Pharm Sci 38:215–223PubMedCrossRefGoogle Scholar
  110. Luke TC, Casadevall A, Watowich SJ et al (2010) Hark back: passive immunotherapy for influenza and other serious infections. Crit Care Med 38:e66–e73PubMedCrossRefGoogle Scholar
  111. Luke TC, Kilbane EM, Jackson JL et al (2006) Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 145:599–609PubMedCrossRefGoogle Scholar
  112. Malakhov MP, Aschenbrenner LM, Smee DF et al (2006) Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection. Antimicrob Agents Chemother 50:1470–1479PubMedCrossRefGoogle Scholar
  113. Marinescu B, Coman C, Iancu AD et al (2009) Evaluation of the efficacy of a specific hyperimmune serum in experimental influenza infection in mice. Roum Arch Microbiol Immunol 68:80–82PubMedGoogle Scholar
  114. Martinez O, Tsibane T, Basler CF (2009) Neutralizing anti-influenza virus monoclonal antibodies: therapeutics and tools for discovery. Int Rev Immunol 28:69–92PubMedCrossRefGoogle Scholar
  115. Matrosovich M, Matrosovich T, Carr J et al (2003) Overexpression of the alpha-2,6-sialyltransferase in MDCK cells increases influenza virus sensitivity to neuraminidase inhibitors. J Virol 77:8418–8425PubMedCrossRefGoogle Scholar
  116. Matrosovich MN, Matrosovich TY, Gray T et al (2004) Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J Virol 78:12665–12667PubMedCrossRefGoogle Scholar
  117. McClellan K, Perry CM (2001) Oseltamivir: a review of its use in influenza. Drugs 61:263–283PubMedCrossRefGoogle Scholar
  118. McCullers JA (2004) Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza. J Infect Dis 190:519–526PubMedCrossRefGoogle Scholar
  119. McCullers JA (2005) Antiviral therapy of influenza. Expert Opin Investig Drugs 14:305–312PubMedCrossRefGoogle Scholar
  120. McCullers JA (2008) Preparing for the next influenza pandemic. Pediatr Infect Dis J 27:S57–S59PubMedCrossRefGoogle Scholar
  121. McKimm-Breschkin JL (2000) Resistance of influenza viruses to neuraminidase inhibitors–a review. Antiviral Res 47:1–17PubMedCrossRefGoogle Scholar
  122. McKimm-Breschkin JL (2002) Neuraminidase inhibitors for the treatment and prevention of influenza. Expert Opin Pharmacother 3:103–112PubMedCrossRefGoogle Scholar
  123. Memoli MJ, Hrabal RJ, Hassantoufighi A et al (2010) Rapid selection of oseltamivir- and peramivir-resistant pandemic H1N1 virus during therapy in 2 immunocompromised hosts. Clin Infect Dis 50:1252–1255PubMedCrossRefGoogle Scholar
  124. Monto AS, Gunn RA, Bandyk MG et al (1979) Prevention of Russian influenza by amantadine. JAMA 241:1003–1007PubMedCrossRefGoogle Scholar
  125. Monto AS, Robinson DP, Herlocher ML et al (1999) Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial. JAMA 282:31–35PubMedCrossRefGoogle Scholar
  126. Morrison D, Roy S, Rayner C et al (2007) A randomized, crossover study to evaluate the pharmacokinetics of amantadine and oseltamivir administered alone and in combination. PLoS ONE 2:e1305PubMedCrossRefGoogle Scholar
  127. Moscona A (2009) Global transmission of oseltamivir-resistant influenza. N Engl J Med 360:953–956PubMedCrossRefGoogle Scholar
  128. Moscona A, Porotto M, Palmer S et al (2010) A recombinant sialidase fusion protein effectively inhibits human parainfluenza viral infection in vitro and in vivo. J Infect Dis 202:234–241PubMedCrossRefGoogle Scholar
  129. Moss RB, Davey RT, Steigbigel RT et al (2010) Targeting pandemic influenza: a primer on influenza antivirals and drug resistance. J Antimicrob Chemother 65:1086–1093PubMedCrossRefGoogle Scholar
  130. Napolitano LM, Park PK, Raghavendran K et al (2010) Nonventilatory strategies for patients with life-threatening 2009 H1N1 influenza and severe respiratory failure. Crit Care Med 38:e74–e90PubMedCrossRefGoogle Scholar
  131. Nelson MI, Simonsen L, Viboud C et al (2009) The origin and global emergence of adamantane resistant A/H3N2 influenza viruses. Virology 388:270–278PubMedCrossRefGoogle Scholar
  132. Nguyen JT, Hoopes JD, Le MH et al (2010) Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains in vitro. PLoS ONE 5:e9332PubMedCrossRefGoogle Scholar
  133. Nguyen JT, Hoopes JD, Smee DF et al (2009) Triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro. Antimicrob Agents Chemother 53:4115–4126PubMedCrossRefGoogle Scholar
  134. Nicholson KG, Aoki FY, Osterhaus AD et al (2000) Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet 355:1845–1850PubMedCrossRefGoogle Scholar
  135. Nishiura H, Castillo-Chavez C, Safan M et al (2009) Transmission potential of the new influenza A(H1N1) virus and its age-specificity in Japan. Euro Surveill 14Google Scholar
  136. O’Keefe BR, Smee DF, Turpin JA et al (2003) Potent anti-influenza activity of cyanovirin-N and interactions with viral hemagglutinin. Antimicrob Agents Chemother 47:2518–2525PubMedCrossRefGoogle Scholar
  137. Orzeck EA, Shi N, Blumentals WA (2007) Oseltamivir and the risk of influenza-related complications and hospitalizations in patients with diabetes. Clin Ther 29:2246–2255PubMedCrossRefGoogle Scholar
  138. Perez-Padilla R, de la Rosa-Zamboni Ponce, de Leon S et al (2009) Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 361:680–689PubMedCrossRefGoogle Scholar
  139. Piedra PA, Schulman KL, Blumentals WA (2009) Effects of oseltamivir on influenza-related complications in children with chronic medical conditions. Pediatrics 124:170–178PubMedCrossRefGoogle Scholar
  140. Pinto LH, Holsinger LJ, Lamb RA (1992) Influenza virus M2 protein has ion channel activity. Cell 69:517–528PubMedCrossRefGoogle Scholar
  141. Raboud JM, Harris M, Rae S et al (2002) Impact of adherence on duration of virological suppression among patients receiving combination antiretroviral therapy. HIV Med 3:118–124PubMedCrossRefGoogle Scholar
  142. Ramisse F, Deramoudt FX, Szatanik M et al (1998) Effective prophylaxis of influenza A virus pneumonia in mice by topical passive immunotherapy with polyvalent human immunoglobulins or F(ab’)2 fragments. Clin Exp Immunol 111:583–587PubMedCrossRefGoogle Scholar
  143. Reichert T, Chowell G, Nishiura H et al (2010) Does glycosylation as a modifier of Original Antigenic Sin explain the case age distribution and unusual toxicity in pandemic novel H1N1 influenza? BMC Infect Dis 10:5PubMedCrossRefGoogle Scholar
  144. Shiraishi K, Mitamura K, Sakai-Tagawa Y et al (2003) High frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza. J Infect Dis 188:57–61PubMedCrossRefGoogle Scholar
  145. Sidwell RW, Bailey KW, Wong MH et al (2005) In vitro and in vivo influenza virus-inhibitory effects of viramidine. Antiviral Res 68:10–17PubMedCrossRefGoogle Scholar
  146. Sidwell RW, Barnard DL, Day CW et al (2007) Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice. Antimicrob Agents Chemother 51:845–851PubMedCrossRefGoogle Scholar
  147. Sleeman K, Mishin VP, Deyde VM et al (2010) In Vitro antiviral activity of favipiravir (T-705) against drug-resistant influenza and 2009 A(H1N1) viruses. Antimicrob Agents Chemother 54:2517–2524PubMedCrossRefGoogle Scholar
  148. Smee DF, Bailey KW, Morrison AC et al (2002) Combination treatment of influenza A virus infections in cell culture and in mice with the cyclopentane neuraminidase inhibitor RWJ-270201 and ribavirin. Chemotherapy 48:88–93PubMedCrossRefGoogle Scholar
  149. Smee DF, Bailey KW, Wong MH et al (2008) Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N. Antiviral Res 80:266–271PubMedCrossRefGoogle Scholar
  150. Smee DF, Hurst BL, Wong MH et al (2010) Effects of the combination of favipiravir (T-705) and oseltamivir on influenza A virus infections in mice. Antimicrob Agents Chemother 54:126–133PubMedCrossRefGoogle Scholar
  151. Smee DF, Wandersee MK, Checketts MB et al (2007) Influenza A (H1N1) virus resistance to cyanovirin-N arises naturally during adaptation to mice and by passage in cell culture in the presence of the inhibitor. Antivir Chem Chemother 18:317–327PubMedGoogle Scholar
  152. Smee DF, Wong MH, Bailey KW et al (2006) Activities of oseltamivir and ribavirin used alone and in combination against infections in mice with recent isolates of influenza A (H1N1) and B viruses. Antivir Chem Chemother 17:185–192PubMedGoogle Scholar
  153. Staschke KA, Colacino JM, Baxter AJ et al (1995) Molecular basis for the resistance of influenza viruses to 4- guanidino-Neu5Ac2en. Virology 214:642–646PubMedCrossRefGoogle Scholar
  154. Stein DS, Creticos CM, Jackson GG et al (1987) Oral ribavirin treatment of influenza A and B. Antimicrob Agents Chemother 31:1285–1287PubMedCrossRefGoogle Scholar
  155. Steinberg KP, Hudson LD, Goodman RB et al (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 354:1671–1684PubMedCrossRefGoogle Scholar
  156. Steinhauer DA, Martin J, Lin YP et al (1996) Studies using double mutants of the conformational transitions in influenza hemagglutinin required for its membrane fusion activity. Proc Natl Acad Sci USA 93:12873–12878PubMedCrossRefGoogle Scholar
  157. Stilianakis NI, Perelson AS, Hayden FG (2002) Drug resistance and influenza pandemics. Lancet 359:1862–1863PubMedCrossRefGoogle Scholar
  158. Straumanis JP, Tapia MD, King JC (2002) Influenza B infection associated with encephalitis: treatment with oseltamivir. Pediatr Infect Dis J 21:173–175PubMedCrossRefGoogle Scholar
  159. Sugaya N, Ohashi Y (2010) Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection. Antimicrob Agents Chemother 54:2575–2582PubMedCrossRefGoogle Scholar
  160. Tai CY, Escarpe PA, Sidwell RW et al (1998) Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071. Antimicrob Agents Chemother 42:3234–3241PubMedGoogle Scholar
  161. Takahashi K, Furuta Y, Fukuda Y et al (2003) In vitro and in vivo activities of T-705 and oseltamivir against influenza virus. Antivir Chem Chemother 14:235–241PubMedGoogle Scholar
  162. Treanor JJ, Hayden FG, Vrooman PS et al (2000) Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA 283:1016–1024Google Scholar
  163. Triana-Baltzer GB, Gubareva LV, Klimov AI et al (2009a) Inhibition of neuraminidase inhibitor-resistant influenza virus by DAS181, a novel sialidase fusion protein. PLoS ONE 4:e7838PubMedCrossRefGoogle Scholar
  164. Triana-Baltzer GB, Gubareva LV, Nicholls JM et al (2009b) Novel pandemic influenza A(H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein. PLoS ONE 4:e7788PubMedCrossRefGoogle Scholar
  165. Van Voris LP, Betts RF, Hayden FG et al (1981) Successful treatment of naturally occurring influenza A/USSR/77 H1N1. JAMA 245:1128–1131PubMedCrossRefGoogle Scholar
  166. von Itzstein M, Dyason JC, Oliver SW et al (1996) A study of the active site of influenza virus sialidase: an approach to the rational design of novel anti-influenza drugs. J Med Chem 39:388–391CrossRefGoogle Scholar
  167. Wang C, Takeuchi K, Pinto LH et al (1993) Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block. J Virol 67:5585–5594PubMedGoogle Scholar
  168. Webby RJ, Webster RG (2003) Are we ready for pandemic influenza? Science 302:1519–1522PubMedCrossRefGoogle Scholar
  169. Welliver R, Monto AS, Carewicz O et al (2001) Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA 285:748–754PubMedCrossRefGoogle Scholar
  170. White NJ, Webster RG, Govorkova EA et al (2009) What is the optimal therapy for patients with H5N1 influenza? PLoS Med 6:e1000091PubMedCrossRefGoogle Scholar
  171. Whitley RJ, Hayden FG, Reisinger KS et al (2001) Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 20:127–133PubMedCrossRefGoogle Scholar
  172. Wingfield WL, Pollack D, Grunert RR (1969) Therapeutic efficacy of amantadine HCl and rimantadine HCl in naturally occurring influenza A2 respiratory illness in man. N Engl J Med 281:579–584PubMedCrossRefGoogle Scholar
  173. Yamashita M, Tomozawa T, Kakuta M et al (2009) CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrob Agents Chemother 53:186–192PubMedCrossRefGoogle Scholar
  174. Yen HL, Herlocher LM, Hoffmann E et al (2005) Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility. Antimicrob Agents Chemother 49:4075–4084PubMedCrossRefGoogle Scholar
  175. Zheng BJ, Chan KW, Lin YP et al (2008) Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus. Proc Natl Acad Sci USA 105:8091–8096PubMedCrossRefGoogle Scholar
  176. Zhou B, Zhong N, Guan Y (2007) Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med 357:1450–1451PubMedCrossRefGoogle Scholar
  177. Zonis Z, Engelhard D, Hindiyeh M et al (2010) Community-acquired oseltamivir-resistant pandemic (H1N1) 2009 in child, Israel. Emerg Infect Dis 16:1045–1046PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Infectious DiseasesSt. Jude Children’s Research HospitalMemphisTN, USA

Personalised recommendations