Preferences help
enabled [disable] Abstract
Number of results
2014 | 61 | 3 | 495-504
Article title

Antivirals - current trends in fighting influenza

Title variants
Languages of publication
Influenza virus infection is a major source of morbidity and mortality worldwide. Due to the variable effectiveness of existing vaccines, especially in the early stages of an epidemic, antiviral drugs represent the first line of defense against the virus. Currently, there are two major classes of anti-influenza drugs approved by the FDA for clinical use: M2 protein inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (zanamivir and oseltamivir). However, increasing resistance to these available influenza antivirals among circulating influenza viruses highlights the need to develop alternative approaches for the prevention and/or treatment of influenza. This review presents an overview of currently available drugs for influenza treatment as well as summarizes some new antiviral strategies that are now being tested covering agents targeting both the viral proteins and the host-virus interaction. We discuss their mechanisms of action, resistance and the therapeutic potential as new antiviral drug for use in future influenza pandemics. Additionally, combination therapy based on these drugs is also described.
Physical description
  • Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdańsk, Poland
  • Department of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdańsk, Poland
  • Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdańsk, Poland
  • Abed Y, Nehme 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.
  • Alves Galvao MG, Rocha Crispino Santos MA, Alves da Cunha AJ (2012) Amantadine and rimantadine for influenza A in children and the elderly. Cochrane Database Syst Rev 1: CD002745.
  • Amorim MJ, Kao RY, Digard P (2013) Nucleozin targets cytoplasmic trafficking of viral ribonucleoprotein-Rab11 complexes in influenza A virus infection. J Virol 87: 4694-4703.
  • Bartlam M, Lou Z, Liu Y, Rao Z (2010) Polymerase structure and function. In Influenza molecular virology. Wang Q, Tao YJ, eds, pp 137152. Caister Academic Press, Norfolk, United Kingdom
  • Belser JA, Lu X, Szretter KJ, Jin X, Aschenbrenner LM, Lee A, Hawley S, Kim do H, Malakhov MP, Yu M, Fang F, Katz JM (2007) DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection. J Infect Dis 196: 1493-1499.
  • Bloom JD, Gong LI, Baltimore D (2010) Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science 328: 1272-1275.
  • Bodian DL, Yamasaki RB, Buswell RL, Stearns JF, White JM, Kuntz ID (1993) Inhibition of the fusion-inducing conformational change of influenza hemagglutinin by benzoquinones and hydroquinones. Biochemistry 32: 2967-2978.
  • Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, Povinelli L, Cox NJ, Klimov AI (2005) Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 366: 1175-1181.
  • Bright RA, Shay D, Bresee J, Klimov A, Cox N, Ortiz J (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 (Reprinted from MMWR, vol. 55, pg 44-46, 2006) JAMA 295: 881-882.
  • CDC (2011) Antiviral agents for the treatment and chemoprophylaxis of Influenza. MMWR Recomm Rep 60: 1.
  • Cheng H, Wan J, Lin MI, Liu Y, Lu X, Liu J, Xu Y, Chen J, Tu Z, Cheng YS, Ding K (2012) Design, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein. J Med Chem 55: 2144-2153.
  • Choi WY, Kim S, Lee N, Kwon M, Yang I, Kim MJ, Cheong SG, Kwon D, Lee JY, Oh HB, Kang C (2009) Amantadine-resistant influenza A viruses isolated in South Korea from 2003 to 2009. Antiviral Res 84: 199-202.
  • Cianci C, Chung TDY, Meanwell N, Putz H, Hagen M, Colonno RJ, Krystal M (1996) Identification of N-hydroxamic acid and N-hydroxy-Imide compounds that inhibit the influenza virus polymerase. Antivir Chem Chemother 7: 353-360.
  • Ciancio BC, Meerhoff TJ, Kramarz P, Bonmarin I, Borgen K, Boucher CA, Buchholz U, Buda S, Dijkstra F, Dudman S, Duwe S, Hauge SH, Hungnes O, Meijer A, Mossong J, Paget WJ, Phin N, van der Sande M, Schweiger B, Nicoll A (2009) Oseltamivir-resistant influenza A(H1N1) viruses detected in Europe during season 2007-2008 had epidemiologic and clinical characteristics similar to co-circulating susceptible A(H1N1) viruses. Euro Surveill 14: pii: 19412.
  • Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A, Jarrossay D, Vachieri SG, Pinna D, Minola A, Vanzetta F, Silacci C, Fernandez-Rodriguez BM, Agatic G, Bianchi S, Giacchetto-Sasselli I, Calder L, Sallusto F, Collins P, Haire LF, Temperton N, Langedijk JP, Skehel JJ, Lanzavecchia A (2011) A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333: 850-856.
  • Davies BE (2010) Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations. J Antimicrob Chemother 65: ii5-ii10.
  • Davies WL, Grunert RR, Haff RF, Mcgahen JW, Neumayer EM, Paulshock M, Watts JC, Wood TR, Hermann EC, Hoffmann CE (1964) Antiviral activity of 1-adamantanamine (amantadine). Science 144: 862-863.
  • Dharan NJ, Gubareva LV, Meyer JJ, Okomo-Adhiambo M, McClinton RC, Marshall SA, St George K, Epperson S, Brammer L, Klimov AI, Bresee JS, Fry AM (2009) Infections with oseltamivir-resistant influenza influenza A(H1N1) virus in the United States. JAMA 301: 1034-1041.
  • Dreyfus C, Laursen NS, Kwaks T, Zuijdgeest D, Khayat R, Ekiert DC, Lee JH, Metlagel Z, Bujny MV, Jongeneelen M, van der Vlugt R, Lamrani M, Korse HJ, Geelen E, Sahin Ö, Sieuwerts M, Brakenhoff JP, Vogels R, Li OT, Poon LL, Peiris M, Koudstaal W, Ward AB, Wilson IA, Goudsmit J, Friesen RH (2012) Highly conserved protective epitopes on influenza B viruses. Science 337: 1343-1348.
  • Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, Goudsmit J, Wilson IA (2009) Antibody recognition of a highly conserved influenza virus epitope. Science 324: 246-251.
  • Ekiert DC, Friesen RH, Bhabha G, Kwaks T, Jongeneelen M, Yu W, Ophorst C, Cox F, Korse HJ, Brandenburg B, Vogels R, Brakenhoff JP, Kompier R, Koldijk MH, Cornelissen LA, Poon LL, Peiris M, Koudstaal W, Wilson IA, Goudsmit J (2011) A highly conserved neutralizing epitope on group 2 influenza A viruses. Science 333: 843-850.
  • Ekiert DC, Kashyap AK, Steel J, Rubrum A, Bhabha G, Khayat R, Lee JH, Dillon MA, O'Neil RE, Faynboym AM, Horowitz M, Horowitz L, Ward AB, Palese P, Webby R, Lerner RA, Bhatt RR, Wilson IA (2012) Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 489: 526-532.
  • Eyer L, Hruska K (2013) Antiviral agents targeting the influenza virus: a review and publication analysis. Veterinarni Medicina 58: 113-185.
  • Fodor E (2013) The RNA polymerase of influenza a virus: mechanisms of viral transcription and replication. Acta Virol 57: 113-122.
  • Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, Nomura N, Egawa H, Minami S, Watanabe Y, Narita H, Shiraki K (2002) In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother 46: 977-981.
  • Furuta Y, Takahashi K, Shiraki K, Sakamoto K, Smee DF, Barnard DL, Gowen BB, Julander JG, Morrey JD (2009) T-705 (favipiravir) and related compounds: novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res 82: 95-102.
  • Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL (2013) Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res 100: 446-454.
  • Ge Q, Filip L, Bai A, Nguyen T, Eisen HN, Chen J (2004) Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc Natl Acad Sci U S A 101: 8676-8681.
  • Gerritz SW, Cianci C, Kim S, Pearce BC, Deminie C, Discotto L, McAuliffe B, Minassian BF, Shi S, Zhu S, Zhai W, Pendri A, Li G, Poss MA, Edavettal S, McDonnell PA, Lewis HA, Maskos K, Mörtl M, Kiefersauer R, Steinbacher S, Baldwin ET, Metzler W, Bryson J, Healy MD, Philip T, Zoeckler M, Schartman R, Sinz M, Leyva-Grado VH, Hoffmann HH, Langley DR, Meanwell NA, Krystal M (2011) Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers. Proc Natl Acad Sci U S A 108: 15366-15371.
  • Gooskens J, Jonges M, Claas EC, Meijer A, van den Broek PJ, Kroes AM (2009) Morbidity and mortality associated with nosocomial transmission of oseltamivir-resistant influenza A(H1N1) virus. JAMA 301: 1042-1046.
  • Gottschalk A (1959) On the mechanism underlying initiation of influenza virus infection. Ergeb Mikrobiol Immunitatsforsch Exp Ther 32: 1-22.
  • Govorkova EA, Fang HB, 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.
  • Guinea R, Carrasco L (1995) Requirement for vacuolar proton-ATPase activity during entry of influenza virus into cells. J Virol 69: 2306-2312.
  • Harada S, Yokomizo K, Monde K, Maeda Y, Yusa K (2007) A broad antiviral neutral glycolipid, fattiviracin FV-8, is a membrane fluidity modulator. Cell Microbiol 9: 196-203.
  • Hayden FG (2006) Antiviral resistance in influenza viruses - implications for management and pandemic response. N Engl J Med 354: 785-788.
  • Hendricks GL, Weirich KL, Viswanathan K, Li J, Shriver ZH, Ashour J, Ploegh HL, Kurt-Jones EA, Fygenson DK, Finberg RW, Comolli JC, Wang JP (2013) Sialylneolacto-N-tetraose c (LSTc)-bearing liposomal decoys capture influenza A virus. J Biol Chem 288: 8061-8073.
  • Herlocher ML, Truscon R, Elias S, Yen HL, Roberts NA, Ohmit SE, Monto AS (2004) Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 190: 1627-1630.
  • Huss M, Wieczorek H (2009) Inhibitors of V-ATPases: old and new players. J Exp Biol 212: 341-346.
  • Ilyushina NA, Hoffmann E, Salomon R, Webster RG, Govorkova EA (2007) Amantadine-oseltamivir combination therapy for H5N1 influenza virus infection in mice. Antivir Ther 12: 363-370.
  • Ilyushina NA, Hay A, Yilmaz N, Boon AC, Webster RG, Govorkova EA (2008) Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice. Antimicrob Agents Chemother 52: 3889-3897.
  • Ison MG, Gnann JW Jr, Nagy-Agren S, Treannor J, Paya C, Steigbigel R, Elliott M, Weiss HL, Hayden FG, NIAID Collaborative Antiviral Study Group (2003) Safety and efficacy of nebulized zanamivir in hospitalized patients with serious influenza. Antivir Ther 8: 183-190.
  • 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.
  • Jeong HJ, Ryu YB, Park SJ, Kim JH, Kwon HJ, Kim JH, Park KH, Rho MC, Lee WS (2009) Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorg Med Chem 17: 6816-6823.
  • 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.
  • Kessler U, Castagnolo D, Pagano M, Deodato D, Bernardini M, Pilger B, Ranadheera C, Botta M (2013) Discovery and synthesis of novel benzofurazan derivatives as inhibitors of influenza A virus. Bioorg Med Chem Lett 23: 5575-5577.
  • Kim WY, Young Suh G, Huh JW, Kim SH, Kim MJ, Kim YS, Kim HR, Ryu YJ, Han MS, Ko YG, Chon GR, Lee KH, Choi SH, Hong SB, Korean Society of Critical Care Medicine H1N1 Collaborative (2011) Triple-combination antiviral drug for pandemic H1N1 influenza virus infection in critically ill patients on mechanical ventilation. Antimicrob Agents Chemother 55: 5703-5709.
  • Kiso M, Kubo S, Ozawa M, Le QM, Nidom CA, Yamashita M, Kawaoka Y (2010) Efficacy of the new neuraminidase inhibitor CS-8958 against H5N1 influenza viruses. PLoS Pathog 6: e1000786.
  • Kolocouris N, Kolocouris A, Foscolos GB, Fytas G, Neyts J, Padalko E, Balzarini J, Snoeck R, Andrei G, De Clercq E (1996) Synthesis and antiviral activity evaluation of some new aminoadamantane derivatives. 2. J Med Chem 39: 3307-3318.
  • Konig R, Stertz S, Zhou Y, Inoue A, Hoffmann HH, Bhattacharyya S, Alamares JG, Tscherne DM, Ortigoza MB, Liang Y, Gao Q, Andrews SE, Bandyopadhyay S, De Jesus P, Tu BP, Pache L, Shih C, Orth A, Bonamy G, Miraglia L, Ideker T, García-Sastre A, Young JA, Palese P, Shaw ML, Chanda SK (2010) Human host factors required for influenza virus replication. Nature 463: 813-817.
  • Koyama K, Takahashi M, Oitate M, Nakai N, Takakusa H, Miura S, Okazaki O (2009) CS-8958, a prodrug of the novel neuraminidase inhibitor R-125489, demonstrates a favourable long-retention profile in the mouse respiratory tract. Antimicrob Agents Chemother 53: 4845-4851.
  • Krumbholz A, Schmidtke M, Bergmann S, Motzke S, Bauer K, Stech J, Durrwald R, Wutzler P, Zell R (2009) High prevalence of amantadine resistance among circulating European porcine influenza A viruses. J Gen Virol 90: 900-908.
  • Lee CM, Weight AK, Haldar J, Wang L, Klibanov AM, Chen J (2012) Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection. Proc Natl Acad Sci USA 109: 20385-20390.
  • Leneva IA, Russell RJ, Boriskin YS, Hay AJ (2009) Characteristics of arbidol-resistant mutants of influenza virus: implications for the mechanism of anti-influenza action of arbidol. Antiviral Res 81: 132-140.
  • Leonov H, Astrahan P, Krugliak M, Arkin IT (2011) How do aminoadamantanes block the influenza M2 channel, and how does resistance develop? J Am Chem Soc 133: 9903-9911.
  • Luo G, Torri A, Harte WE, Danetz S, Cianci C, Tiley L, Day S, Mullaney D, Yu KL, Ouellet C, Dextraze P, Meanwell N, Colonno R, Krystal M (1997) Molecular mechanism underlying the action of a novel fusion inhibitor of influenza A virus. J Virol 71: 4062-4070.
  • Lv HM, Guo XL, Gu RX, Wei DQ (2011) Free energy calculations and binding analysis of two potential anti- influenza drugs with Polymerase basic protein-2 (PB2). Protein Pept Lett 18: 1002-1009.
  • Macdonald SJ, Cameron R, Demaine DA, Fenton RJ, Foster G, Gower D, Hamblin JN, Hamilton S, Hart GJ, Hill AP, Inglis GG, Jin B, Jones HT, McConnell DB, McKimm-Breschkin J, Mills G, Nguyen V, Owens IJ, Parry N, Shanahan SE, Smith D, Watson KG, Wu WY, 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.
  • Madren LK, Shipman C, Hayden FG (1995) In vitro inhibitory effects of combinations of anti-influenza agents. Antiviral Chem Chemother 6: 109-113.
  • Malakhov MP, Aschenbrenner LM, Smee DF, Wandersee MK, Sidwell RW, Gubareva LV, Mishin VP, Hayden FG, Kim DH, Ing A, Campbell ER, Yu M, Fang F (2006) Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection. Antimicrob Agents Chemother 50: 1470-1479.
  • Marjuki H, Mishin VP, Chesnokov AP, De La Cruz JA, Fry AM, Villanueva J, Gubareva LV (2014) An investigational antiviral drug, DAS181, effectively inhibits replication of zoonotic influenza A virus subtype H7N9 and protects mice from lethality. J Infect Dis Epub ahead of print.
  • Martinez O, Tsibane T, Basler CF (2009) Neutralizing anti-influenza virus monoclonal antibodies: therapeutics and tools for discovery. Int Rev Immunol 28: 69-92.
  • Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD (2004) Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J Virol 78: 12665-12667.
  • Matsubara T, Onishi A, Saito T, Shimada A, Inoue H, Taki T, Nagata K, Okahata Y, Sato T (2010) Sialic acid-mimic peptides as hemagglutinin inhibitors for anti-influenza therapy. J Med Chem 53: 4441-4449.
  • Miller M, Vibound C, Simonsen L, Olson DR, Russell C (2009) Mortality and morbidity burden associated with A/H1N1 pdm influenza virus: Who is likely to be infected, experience clinical symptoms, or die from the H1N1 pdm 2009 virus? PLoSCurr 1: RRN1013.
  • Mishin VP, Hayden FG, Gubareva LV (2005) Susceptibilities of antiviral-resistant influenza viruses to novel neuraminidase inhibitors. Antimicrob Agents Chemother 49: 4515-4520.
  • Muratore G, Goracci L, Mercorelli B, Foeglein Á, Digard P, Cruciani G, Palù G, Loregian A (2012a) Small molecule inhibitors of influenza A and B viruses that act by disrupting subunit interactions of the viral polymerase. Proc Natl Acad Sci U S A 109: 6247-6252.
  • Muratore G, Mercorelli B, Goracci L, Cruciani G, Digard P, Palù G, Loregian A (2012b) Human cytomegalovirus inhibitor AL18 also possesses activity against influenza A and B viruses. Antimicrob Agents Chemother 56: 6009-6013.
  • Nguyen JT, Hoopes JD, Smee DF, Prichard MN, Driebe EM, Engelthaler DM, Le MH, Keim PS, Spence RP, Went GT (2009) Triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro. Antimicrob Agents Chemother 53: 4115-4126.
  • Nguyen JT, Smee DF, Barnard DL, Julander JG, Gross M, de Jong MD, Went GT (2012) Efficacy of combined therapy with amantadine, oseltamivir, and ribavirin in vivo against susceptible and amantadine-resistant influenza A viruses. PLoS One 7: e31006.
  • Nicholls JM, Lai J, Garcia JM (2012) Investigating the interaction between influenza and sialic acid: Making and breaking the link. In Influenza virus sialidase - a drug discovery target. von Itzstein M, ed, pp 31-47. Springer, Basel.
  • Ochiai H, Sakai S, Hirabayashi T, Shimizu Y, Terasawa K (1995) Inhibitory effect of bafilomycin A1, a specific inhibitor of vacuolar-type proton pump, on the growth of influenza A and B viruses in MDCK cells. Antiviral Res 27: 425-430.
  • Okuno Y, Isegawa Y, Sasao F, Ueda S (1993) A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J Virol 67: 2552-2558.
  • Ooi EE, Chew JS, Loh JP, Chua RC (2006) In vitro inhibition of human influenza A virus replication by chloroquine. Virol J 3: 39.
  • Pagano M, Castagnolo D, Bernardini M, Fallacara AL, Laurenzana I, Deodato D, Kessler U, Pilger B, Stergiou L, Strunze S, Tintori C, Botta M (2014) The fight against the influenza A virus H1N1: synthesis, molecular modeling, and biological evaluation of benzofurazan derivatives as viral RNA polymerase inhibitors. Chem Med Chem 9: 129-150.
  • Paton NI, Lee L, Xu Y, Ooi EE, Cheung YB, Archuleta S, Wong G, Wilder-Smith A (2011) Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial. Lancet Infect Dis 11: 677-683.
  • Pizzorno A, Bouhy X, Abed Y, Boivin G (2011) Generation and characterization of recombinant pandemic influenza A (H1N1) viruses resistant to neuraminidase inhibitors. J Infect Dis 203: 25-31.
  • Plotch SJ, O'Hara B, Morin J, Palant O, LaRocque J, Bloom JD, Lang SA Jr, DiGrandi MJ, Bradley M, Nilakantan R, Gluzman Y (1999) Inhibition of influenza A virus replication by compounds interfering with the fusogenic function of the viral hemagglutinin. J Virol 73: 140-151.
  • Portela A, Digard P (2002) The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol 83: 723-734.
  • Prabhu N, Prabakaran M, Ho HT, Velumani S, Qiang J, Goutama M, Kwang J (2009) Monoclonal antibodies against the fusion peptide of hemagglutinin protect mice from lethal influenza A virus H5N1 infection. J Virol 83: 2553-2562.
  • Rajasekaran D, Palombo EA, Chia Yeo T, Lim Siok Ley D, Lee Tu C, Malherbe F, Grollo L (2013) Identification of traditional medicinal plant extracts with novel anti-influenza activity. PLoS One 8: e79293.
  • Samson M, Pizzorno A, Abed Y, Boivin G (2013) Influenza virus resistance to neuraminidase inhibitors. Antiviral Res 98: 174-185.
  • Schulman JL, Palese P (1975) Susceptibility of different strains of influenza A virus to inhibitory effects of 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA). Virology 63: 98-104.
  • Semenova NP, Prokudina EN, Livov DK, Nebol'sin VE (2010) Effect of the antiviral drug Ingaviruin on intracellular transformations and import into the nucleus of influenza A virus nucleocapsid protein. Vopr Virusol 55: 17-20.
  • Sheu TG, Fry AM, Garten RJ, Deyde VM, Shwe T, Bullion L, Peebles PJ, Li Y, Klimov AI, Gubareva LV (2010) Dual resistance to adamantanes and oseltamivir among seasonal influenza A(H1N1) viruses: 2008-2010. J Infect Dis 203: 13-17.
  • Sidwell RW, Smee DF (2002) Peramivir (BCX-1812, RWJ-270201): potential new therapy for influenza. Expert Opin Investig Drugs 11: 859-869.
  • Sidwell RW, Bailey KW, Wong MH, Barnard DL, Smee DF (2005) In vitro and in vivo influenza virus-inhibitory effects of viramidine. Antiviral Res 68: 10-17.
  • Stamatiou G1, Kolocouris A, Kolocouris N, Fytas G, Foscolos GB, Neyts J, De Clercq E (2001) Novel 3-(2-adamantyl)pyrrolidines with potent activity against influenza A virus-identification of aminoadamantane derivatives bearing two pharmacophoric amine groups. Bioorg Med Chem Lett 11: 2137-2142.
  • Steinhauer DA (2010) Influenza A virus haemagglutinin glycoproteins. In Influenza molecular virology. Wang Q, Tao YJ, eds, pp 69-109. Caister Academic Press, Norfolk, United Kingdom
  • Suzuki T, Takahashi T, Guo CT, Hidari KI, Miyamoto D, Goto H, Kawaoka Y, Suzuki Y (2005) Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication. J Virol 79: 11705-11715.
  • Tado M, Abe T, Hatta T, Ishikawa M, Nakada S, Yokota T, Takaku H (2001) Inhibitory effect of modified 5'-capped short RNA fragments on influenza virus RNA polymerase gene expression. Antivir Chem Chemother 12: 353-358.
  • Tarbet EB, Maekawa M, Furuta Y, Babu YS, Morrey JD, Smee DF (2012) Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009 (H1N1) virus infections in mice. Antiviral Res 94: 103-110.
  • Tarbet EB, Vollmer AH, Hurst BL, Barnard DL, Furuta Y, Smee DF (2013) In vitro activity of favipiravir and neuraminidase inhibitor combinations against oseltamivir-sensitive and oseltamivir-resistant pandemic influenza A (H1N1) virus. Arch Virol Epub ahead of print.
  • Teissier E, Zandomeneghi G, Loquet A, Lavillette D, Lavergne JP, Montserret R, Cosset FL, Bockmann A, Meier BH, Penin F, Pecheur EI (2011) Mechanism of inhibition of enveloped virus membrane fusion by the antiviral drug arbidol. PLoS One 6: e15874.
  • Terabayashi T, Morita M, Ueno M, Nakamura T, Urashima T (2006) Inhibition of influenza-virus-induced cytopathy by sialylglycoconjugates. Carbohydr Res 341: 2246-2253.
  • Thomson R, von Itzstein M (2012) The development of carbohydrate-based influenza virus sialidase inhibitors. In Influenza virus sialidase - a drug discovery target. von Itzstein M, ed, pp 31-47. Springer, Basel.
  • Tomassini JE, Selnick H, Davies ME, Armstrong ME, Baldwin J, Bourgeois M, Hastings J, Hazuda D, Lewis J, McClements W, Ponticello G, Radzilowski E, Smith G, Tebben A, Wolfe A (1994) Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds. Antimicrob Agents Chemother 38: 2827-2837.
  • Tomassini JE, Davies ME, Hastings JC, Lingham R, Mojena M, Raghoobar SL, Singh SB, Tkacz JS, Goetz MA (1996) A novel antiviral agent which inhibits the endonuclease of influenza viruses. Antimicrob Agents Chemother 40: 1189-1193.
  • Tompkins SM, Lo CY, Tumpey TM, Epstein SL (2004) Protection against lethal influenza virus challenge by RNA interference in vivo. Proc Natl Acad Sci U S A 101: 8682-8686.
  • Triana-Baltzer GB, Gubareva LV, Nicholls JM, Pearce MB, Mishin VP, Belser JA, Chen LM, Chan RW, Chan MC, Hedlund M, Larson JL, Moss RB, Katz JM, Tumpey TM, Fang F (2009) Novel pandemic influenza A(H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein. PLoS One 4: e7788.
  • Vanderlinden E, Goktas F, Cesur Z, Froeyen M, Reed ML, Russell CJ, Cesur N, Naesens L (2010) Novel inhibitors of influenza virus fusion: structure-activity relationship and interaction with the viral hemagglutinin. J Virol 84: 4277-4288.
  • von Itzstein M, Wu WY, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, et al. (1993) Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363: 418-423.
  • von Itzstein M, Wu WY, Jin B (1994) The synthesis of 2,3-didehydro-2,4-dideoxy-4-guanidinyl-N-acetylneuraminic acid: a potent influenza virus sialidase inhibitor. Carbohydr Res 259: 301-305.
  • von Itzstein M (2007) The war against influenza: discovery and development of sialidase inhibitors. Nat Rev Drug Discov 6: 967-974.
  • von Itzstein M, Thomson R (2009) Anti-influenza drugs: the development of sialidase inhibitors. Handb Exp Pharmacol 189: 111-154.
  • 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.
  • Wang J, Ma C, Fiorin G, Carnevale V, Wang T, Hu F, Lamb RA, Pinto LH, Hong M, Klein ML, DeGrado WF (2011) Molecular dynamics simulation directed rational design of inhibitors targeting drug-resistant mutants of influenza A virus M2. J Am Chem Soc 133: 12834-12841.
  • Wang J, Wu Y, Ma C, Fiorin G, Wang J, Pinto LH, Lamb RA, Klein ML, Degrado WF (2013a) Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus. Proc Natl Acad Sci U S A 110: 1315-1320.
  • Wang J, Ma C, Wang J, Jo H, Canturk B, Fiorin G, Pinto LH, Lamb RA, Klein ML, DeGrado WF (2013b) Discovery of novel dual inhibitors of the wild-type and the most prevalent drug-resistant mutant, S31N, of the M2 proton channel from influenza A virus. J Med Chem 56: 2804-2812.
  • 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, Wu WY (2004) Highly potent and long-acting trimeric and tetrameric inhibitors of influenza virus neuraminidase. Bioorg Med Chem Lett 14: 1589-1592.
  • Wei G, Meng W, Guo H, Pan W, Liu J, Peng T, Chen L, Chen CY (2011) Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein. PLoS One 6: e28309.
  • Weight AK, Haldar J, Alvarez de Cienfuegos L, Gubareva LV, Tumpey TM, Chen J, Klibanov AM (2011) Attaching zanamivir to a polymer markedly enhances its activity against drug-resistant strains of influenza a virus. J Pharm Sci 100: 831-835.
  • Whittle JR, Zhang R, Khurana S, King LR, Manischewitz J, Golding H, Dormitzer PR, Haynes BF, Walter EB, Moody MA, Kepler TB, Liao HX, Harrison SC (2011) Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Natl Acad Sci U S A 108: 14216-14221.
  • WHO (2010) Clinical Aspects of Pandemic (H1N1) 2009 Influenza. N Engl J Med 362: 1708-1719.
  • Wilson SZ, Knight V, Wyde PR, Drake S, Couch RB (1980) Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice. Antimicrob Agents Chemother 17: 642-648.
  • Wolf MC, Freiberg AN, Zhang T, Akyol-Ataman Z, Grock A, Hong PW, Li J, Watson NF, Fang AQ, Aguilar HC, Porotto M, Honko AN, Damoiseaux R, Miller JP, Woodson SE, Chantasirivisal S, Fontanes V, Negrete OA, Krogstad P, Dasgupta A, Moscona A, Hensley LE, Whelan SP, Faull KF, Holbrook MR, Jung ME, Lee B (2010) A broad-spectrum antiviral targeting entry of enveloped viruses. Proc Natl Acad Sci U S A 107: 3157-3162.
  • Wolkerstorfer A, Kurz H, Bachhofner N, Szolar OH (2009) Glycyrrhizin inhibits influenza A virus uptake into the cell. Antiviral Res 83: 171-178.
  • Yen HL, Hoffmann E, Taylor G, Scholtissek C, Monto AS, Webster RG, Govorkova EA (2006) Importance of neuraminidase active-site residues to the neuraminidase inhibitor resistance of influenza viruses. J Virol 80: 8787-8795.
  • Yen HL, 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.
  • Yoshida R, Igarashi M, Ozaki H, Kishida N, Tomabechi D, Kida H, Ito K, Takada A (2009) Cross-protective potential of a novel monoclonal antibody directed against antigenic site B of the hemagglutinin of influenza A viruses. PLoS Pathog 5: e1000350.
  • Yoshimoto J, Kakui M, Iwasaki H, Fujiwara T, Sugimoto H, Hattori N (1999) Identification of a novel HA conformational change inhibitor of human influenza virus. Arch Virol 144: 865-878.
  • Zarubaev VV, Golod EL, Anfimov PM, Shtro AA, Saraev VV, Gavrilov AS, Logvinov AV, Kiselev OI (2010) Synthesis and anti-viral activity of azolo-adamantanes against influenza A virus. Bioorg Med Chem 18: 839-848.
  • Zhao X, Li C, Zeng S, Hu W (2011) Discovery of highly potent agents against influenza A virus. Eur J Med Chem 46: 52-57.
  • Zhao X, Jie Y, Rosenberg MR, Wan J, Zeng S, Cui W, Xiao Y, Li Z, Tu Z, Casarotto MG, Hu W (2012) Design and synthesis of pinanamine derivatives as anti-influenza A M2 ion channel inhibitors. Antiviral Res 96: 91-99.
  • Zhou H, Jin M, Yu Z, Xu X, Peng Y, Wu H, Liu J, Liu H, Cao S, Chen H (2007) Effective small interfering RNAs targeting matrix and nucleocapsid protein gene inhibit influenza A virus replication in cells and mice. Antiviral Res 76: 186-193.
  • Zhu L, Li Y, Li S, Li H, Qiu Z, Lee C, Lu H, Lin X, Zhao R, Chen L, Wu JZ, Tang G, Yang W (2011) Inhibition of influenza A virus (H1N1) fusion by benzenesulfonamide derivatives targeting viral hemagglutinin. PLoS One 6: e29120.
  • Zoidis G, Fytas C, Papanastasiou I, Foscolos GB, Fytas G, Padalko E, De Clercq E, Naesens L, Neyts J, Kolocouris N (2006) Heterocyclic rimantadine analogues with antiviral activity. Bioorg Med Chem 14: 3341-3348.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.