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Virology Journal
Published in: Virology Journal 1/2014

Open Access 01-12-2014 | Review

Emerging antiviral resistant strains of influenza A and the potential therapeutic targets within the viral ribonucleoprotein (vRNP) complex

Authors: Alicia M Davis, Bryan J Chabolla, Laura L Newcomb

Published in: Virology Journal | Issue 1/2014

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Abstract

Emerging antiviral resistant strains of influenza A virus are greatly limiting the therapies available to stop aggressive infections. Genome changes that confer resistance to the two classes of approved antivirals have been identified in circulating influenza A viruses. It is only a matter of time before the currently approved influenza A antivirals are rendered ineffective, emphasizing the need for additional influenza antiviral therapies. This review highlights the current state of antiviral resistance in circulating and highly pathogenic influenza A viruses and explores potential antiviral targets within the proteins of the influenza A virus ribonucleoprotein (vRNP) complex, drawing attention to the viral protein activities and interactions that play an indispensable role in the influenza life cycle. Investigation of small molecule inhibition, accelerated by the use of crystal structures of vRNP proteins, has provided important information about viral protein domains and interactions, and has revealed many promising antiviral drug candidates discussed in this review.
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Literature
1.
Reid AH, Taubenberger JK: The origin of the 1918 pandemic influenza virus: a continuing enigma. J Gen Virol 2003, 84: 2285-2292. 10.1099/vir.0.19302-0PubMedCrossRef
2.
3.
4.
Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, Basta S, O’Neill R, Schickli J, Palese P, Henklein P, Bennink JR, Yewdell JW: A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 2001, 7: 1306-1312. 10.1038/nm1201-1306PubMedCrossRef
5.
Wise HM, Foeglein A, Sun J, Dalton RM, Patel S, Howard W, Anderson EC, Barclay WS, Digard P: A complicated message: identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA. J Virol 2009, 83: 8021-8031. 10.1128/JVI.00826-09PubMedPubMedCentralCrossRef
6.
Jagger BW, Wise H, Kash JC, Walters KA, Wills NM, Xiao YL, Dunfee RL, Schartzman LM, Ozinsky A, Bell GL, Dalton RM, Lo A, Efstathiou S, Atkins JF, Firth AE, Taubenberger JK, Digard P: An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science 2012, 337: 199-204. 10.1126/science.1222213PubMedPubMedCentralCrossRef
7.
Muramoto Y, Noda T, Kawakami E, Akkina R, Kawaoka Y: Identification of novel influenza A virus proteins translated from PA mRNA. J Virol 2012, 87: 2455-2462.PubMedCrossRef
8.
Pinto LH, Holsinger LJ, Lamb RA: Influenza virus M 2 protein has ion channel activity. Cell 1992, 69: 517-528. 10.1016/0092-8674(92)90452-IPubMedCrossRef
9.
Hay AJ, Wolstenholm AJ, Skehel JJ, Smith MH: The molecular basis of the specific anti-influenza action of amantadine. EMBO J 1985, 4: 3021-3024.PubMedPubMedCentral
10.
Jing X, Ma C, Ohigashi Y, Oliveria FA, Jardetzky TS, Pinto LH, Lamb RA: Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel. Proc Natl Acad Sci U S A 2008, 105: 10967-10972. 10.1073/pnas.0804958105PubMedPubMedCentralCrossRef
11.
Davis AR, Bos TJ, Nayak DP: Active influenza virus neuraminidase is expressed in monkey cells from cDNA cloned in simian virus 40 vectors. Proc Natl Acad Sci U S A 1983, 80: 3976-3980. 10.1073/pnas.80.13.3976PubMedPubMedCentralCrossRef
12.
Meindl P, Bodo G, Palese P, Schulman J, Tuppy H: Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology 1974, 58: 457-463. 10.1016/0042-6822(74)90080-4PubMedCrossRef
13.
Palese P, Compans RW: Inhibition of influenza and parainfluenza virus replication in tissue culture by 2-deoxy-2, 3-dehydro-N-trifluoracetylneuraminic acid (FANA). Virology 1974, 59: 490-498. 10.1016/0042-6822(74)90458-9PubMedCrossRef
14.
Holsinger LJ, Nichani D, Pinto LH, Lamb RA: Influenza A virus M2 ion channel protein: a structure-function analysis. J Virol 1984, 68: 1551-1563.
15.
Abed Y, Goyette N, Boivin G: Generation and characterization of recombinant influenza A (H1N1) viruses harboring amantadine resistance mutations. Antimicrob Agents Chemother 2005, 49: 556-559. 10.1128/AAC.49.2.556-559.2005PubMedPubMedCentralCrossRef
16.
17.
Tang JW, Ngai KL, Wong JC, Lam WY, Chan PK: Emergence of adamantane-resistant influenza A (H3N2) viruses in Hong Kong between 1997 and 2006. J Med Virol 2008, 80: 895-901. 10.1002/jmv.21155PubMedCrossRef
18.
Chen Y, Liang W, Yang S, Wu N, Gao H, Sheng J, Yao H, Wo J, Fang Q, Cui D, Li Y, Yao X, Zhang Y, Wu H, Zheng S, Diao H, Xia S, Zhang Y, Chan KH, Tsoi HW, Teng JL, Song W, Wang P, Lau SY, Zheng M, Chan JF, To KK, Chen H, Li L, Yuen KY: Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet 2013, 381: 1916-1925. 10.1016/S0140-6736(13)60903-4PubMedCrossRef
19.
20.
21.
Deyde VM, Sheu TG, Trujillo AA, Okomo-Adhiambo M, Garten R, Klimov AI, Gubareva LV: Detection of molecular markers of drug resistance in 2009 pandemic influenza A (H1N1) viruses by pyrosequencing. Antimicrob Agents Chemother 2010, 54: 1102-1110. 10.1128/AAC.01417-09PubMedPubMedCentralCrossRef
22.
Pizzorno A, Abed Y, Bouhy X, Beaulieu É, Mallett C, Russell R, Boivin G: Impact of mutations at residue I223 of the neuraminidase protein on the resistance profile, replication level, and virulence of the 2009 pandemic influenza virus. Antimicrob Agents Chemother 2012, 56: 1208-1214. 10.1128/AAC.05994-11PubMedPubMedCentralCrossRef
23.
van der Vries E, Kroeze EJV, Stittelaar KJ, Linster M, Van der Linden A, Schrauwen EJ, Leijten LM, van Amoerogen G, Schutten M, Kuiken T, Osterhaus AD, Fouchier RA, Boucher CA, Herfst S: Multidrug resistant 2009 A/H1N1 influenza clinical isolate with a neuraminidase I223R mutation retains its virulence and transmissibility in ferrets. PLoS pathogens 2011, 7: e1002276. 10.1371/journal.ppat.1002276PubMedPubMedCentralCrossRef
24.
Baz M, Abed Y, Papenbug J, Bouhy X, Hamelin ME, Boivin G: Emergenge of oseltamivir-resistant pandemic H1N1 virus during prophylaxis. Engl J Med 2009, 361: 2296-2297. 10.1056/NEJMc0910060CrossRef
25.
Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y: Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 2004, 364: 759-765. 10.1016/S0140-6736(04)16934-1PubMedCrossRef
26.
27.
Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, Zhao X, Zhou L, Li X, Zou S, Zhang Y, Yang L, Guo J, Dong J, Li Q, Dong L, et al.: Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 2013, 368: 1888-1897. 10.1056/NEJMoa1304459PubMedCrossRef
28.
Hai R, Schmolke M, Leyva-Grado VH, Thangavel RR, Margine I, Jaffe ER, Krammer F, Solòrzano A, Carcia-Sastre A, Palese P, Bouvier NM: Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility. Nat Commun 2013, 4: 2854.PubMedPubMedCentralCrossRef
29.
Hurt AC, Selleck P, Komadina N, Shaw R, Brown L, Barr IG: Susceptibility of highly pathogenic A (H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes. Antivir Res 2007, 73: 228-231. 10.1016/j.antiviral.2006.10.004PubMedCrossRef
30.
Plotch SJ, Bouloy M, Ulmanen I, Krug RM: A unique cap (m 7 GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell 1981, 23: 847-858. 10.1016/0092-8674(81)90449-9PubMedCrossRef
31.
Yuan P, Bartlam M, Lou Z, Chen S, Zhou J, He X, Lv Z, Ge R, Li X, Deng T, Fodor E, Rao Z, Liu Y: Crystral structure of an avian influenza polymerase PA N reveals an endonuclease active site. Nature 2009, 458: 909-913. 10.1038/nature07720PubMedCrossRef
32.
Dias A, Bouvier D, Crépin T, McCarthy AA, Hart DJ, Baudin F, Cusack S, Ruigrok RW: The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 2009, 458: 914-918. 10.1038/nature07745PubMedCrossRef
33.
Li ML, Rao P, Krug RM: The active sites of the influenza cap-dependent endonuclease are on different polymerase subunits. EMBO J 2001, 20: 2078-2086. 10.1093/emboj/20.8.2078PubMedPubMedCentralCrossRef
34.
Poon LL, Pritlove DC, Fodor E, Brownlee GG: Direct evidence that the poly (A) tail of influenza A virus mRNA is synthesized by reiterative copying of a U track in the virion RNA template. J Virol 1999, 73: 3473-3476.PubMedPubMedCentral
35.
Shapiro GI, Krug RM: Influenza Virus RNA Replication In Vitro: Synthesis of Viral Template RNAs and Virion RNAs in the Absence of an Added Primer. J Virol 1988, 62: 2285-2290.PubMedPubMedCentral
36.
Jorba N, Coloma R, Ortín J: Genetic trans-complementation establishes a new model for influenza virus RNA transcription and replication. PLoS pathogens 2009, 5: e1000462. 10.1371/journal.ppat.1000462PubMedPubMedCentralCrossRef
37.
Beaton AR, Krug RM: Transcription antitermination during influenza viral template RNA synthesis requires the nucleocapsid protein and the absence of a 5’capped end. Proc Natl Acad Sci USA 1986, 83: 6282-6286. 10.1073/pnas.83.17.6282PubMedPubMedCentralCrossRef
38.
Honda A, Ueda K, Nagata K, Ishihama A: RNA Polymerase of Influenza Virus: Role of NP in RNA Chain Elongation. J Biochem 1988, 104: 1021-1026.PubMed
39.
Ye Q, Krug RM, Tao YJ: The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA. Nature 2006, 444: 1078-1082. 10.1038/nature05379PubMedCrossRef
40.
Ye Q, Guu TS, Mata DA, Kuo RL, Smith B, Krug RM, Tao YJ: Biochemical and structural evidence in support of a coherent model for the formation of the double-helical influenza A virus ribonucleoprotein. mBio 2012, 4: e00467-12.PubMedPubMedCentralCrossRef
41.
Kao RY, Yang D, Lau LS, Tsui WH, Hu L, Dai J, Chan MP, Chan CM, Wang P, Zheng BJ, Sun J, Huang JD, Madar J, Chen G, Chen H, Guan Y, Yuen KY: Identification of influenza A nucleoprotein as an antiviral target. Nat Biotechnol 2010, 28: 600-605. 10.1038/nbt.1638PubMedCrossRef
42.
Shen YF, Chen Y, Chu SY, Lin MI, Hsu HT, Wu PY, Wu CJ, Liu HW, Lin FY, Lin G, Hsu PH, Yang AS, Cheng YS, Wu YT, Wong CH, Tsai MD: E339… R416 salt bridge of nucleoprotein as a feasible target for influenza virus inhibitors. Proc Nat Acad Sci USA 2011, 108: 16515-16520. 10.1073/pnas.1113107108PubMedPubMedCentralCrossRef
43.
Biswas SK, Boutz PL, Nayak DP: Influenza virus nucleoprotein interacts with influenza virus polymerase proteins. J Virol 1988, 72: 5493-5501.
44.
Avalos RT, Yu Z, Nayak DP: Association of influenza virus NP and M1 proteins with cellular cytoskeletal elements in influenza virus-infected cells. J Virol 1997, 71: 2947-2958.PubMedPubMedCentral
45.
Portela A, Digard P: The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol 2002, 83: 723-734.PubMedCrossRef
46.
Newcomb LL, Kuo RL, Ye Q, Jiang Y, Tao YJ, Krug RM: Interaction of the influenza a virus nucleocapsid protein with the viral RNA polymerase potentiates unprimed viral RNA replication. J Virol 2009, 83: 29-36. 10.1128/JVI.02293-07PubMedPubMedCentralCrossRef
47.
Ng AK, Chan WH, Choi ST, Lam MK, Lau KF, Chan PK, Au SW, Fodor E, Shaw PC: Influenza polymerase activity correlates with the strength of interaction between nucleoprotein and PB2 through the host-specific residue K/E627. PLoS ONE 2012, 7: e36415. 10.1371/journal.pone.0036415PubMedPubMedCentralCrossRef
48.
Li Z, Watanabe T, Hatta M, Watanabe S, Nanbo A, Ozawa M, Kakugawa S, Shimojima M, Yamada S, Neumann G, Kawaoka Y: Mutational analysis of conserved amino acids in the influenza A virus nucleoprotein. J Virol 2009, 83: 4153-4162. 10.1128/JVI.02642-08PubMedPubMedCentralCrossRef
49.
Subbarao EK, London W, Murphy BR: A single amino acid in the PB2 gene of the influenza A virus is a determinant of host range. J Virol 1993, 67: 1761-1764.PubMedPubMedCentral
50.
Kuzuhara T, Kise D, Yoshida H, Horita T, Murazaki Y, Nishimura A, Echigo N, Utsunomiya H, Tsuge H: Structural basis of the influenza A virus RNA polymerase PB2 RNA-binding domain containing the pathogenicity-determinant lysine 627 residue. J Biol Chem 2009, 284: 6855-6860. 10.1074/jbc.C800224200PubMedPubMedCentralCrossRef
51.
Marklund JK, Ye Q, Dong J, Tao YJ, Krug RM: Sequence in the influenza A virus nucleoprotein required for viral polymerase binding and RNA synthesis. J Virol 2012, 86: 7292-7297. 10.1128/JVI.00014-12PubMedPubMedCentralCrossRef
52.
Arranz R, Coloma R, Chichón J, Conesa JJ, Carrascosa JL, Valpuesta JM, Ortín J, Martĺn-Benito J: The Structure of Native Influenza Virion Ribonucleoproteins. Science 2012, 338: 1634-1637. 10.1126/science.1228172PubMedCrossRef
53.
Gorman OT, Bean WJ, Kawaoka Y, Webster RG: Evolution of the nucleoprotein gene of influenza A virus. J Virol 1990, 64: 1487-97.PubMedPubMedCentral
54.
Zhao C, Lou Z, Guo Y, Ma M, Chen Y, Liang S, Zhang L, Chen S, Li X, Liu Y, Bartlam M, Rao Z: Nucleoside monophosphate complex structures of the endonuclease domain from the influenza virus polymerase PA subunit reveal the substrate binding site inside the catalytic center. J Virol 2009, 83: 9024-9030. 10.1128/JVI.00911-09PubMedPubMedCentralCrossRef
55.
Hara K, Schmidt FI, Crow M, Brownlee GG: Amino acid residues in the N-terminal region of the PA subunit of influenza A virus RNA polymerase play a critical role in protein stability, endonuclease activity, cap binding, and virion RNA promoter binding. J Virol 2006, 80: 7789-7798. 10.1128/JVI.00600-06PubMedPubMedCentralCrossRef
56.
Deng T, Vreede FT, Brownlee GG: Different De Novo Initiation Strategies Are Used by Influenza Virus RNA Polymerase on Its cRNA and Viral RNA Promoters during Viral RNA Replication. J. Virol 2006, 80: 2337-2348. 10.1128/JVI.80.5.2337-2348.2006PubMedPubMedCentralCrossRef
57.
Maier H, Kashiwagi T, Hara K, Brownlee GG: Differential role of the influenza A virus polymerase PA subunit for vRNA and cRNA promoter binding. Virology 2008, 370: 194-204. 10.1016/j.virol.2007.08.029PubMedCrossRef
58.
Fetcher P, Mingay L, Sharps J, Chambers A, Fodor E, Brownlee GG: Two aromatic residues in the PB2 subunit of influenza A RNA polymerase are crucial for cap binding. J Biol Chem 2003, 278: 20381-20388. 10.1074/jbc.M300130200CrossRef
59.
Guilligay D, Tarendeau F, Resa-Infante P, Coloma R, Crepin T, Sehr P, Lewis J, Ruigrok RW, Ortin J, Hart DJ, Cusack S: The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat Struct Mol Bio 2008, 15: 500-506. 10.1038/nsmb.1421CrossRef
60.
Massin P, van der Werf S, Naffakh N: Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. J Virol 2001, 75: 5398-5404. 10.1128/JVI.75.11.5398-5404.2001PubMedPubMedCentralCrossRef
61.
Shinya K, Hamm S, Hatta M, Ito H, Ito T, Kawaoka Y: PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice. Virology 2004, 320: 258-266. 10.1016/j.virol.2003.11.030PubMedCrossRef
62.
Labadie K, Dos Santos Afonso E, Rameix-Welti MA, Van Der Werf S, Naffakh N: Host-range determinants on the PB2 protein of influenza A viruses control the interaction between the viral polymerase and nucleoprotein in human cells. Virology 2007, 362: 271-282. 10.1016/j.virol.2006.12.027PubMedCrossRef
63.
Tarendeau F, Crepin T, Guilligay D, Ruigrok RW, Cusack S, Hart DJ: Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit. PLoS Pathog 2008, 4: e1000136. 10.1371/journal.ppat.1000136PubMedPubMedCentralCrossRef
64.
González S, Ortin J: Characterization of influenza virus PB1 protein binding to viral RNA: two separate regions of the protein contribute to the interaction domain. J Virol 1999, 73: 631-637.PubMedPubMedCentral
65.
Perez DR, Donis RO: A 48-amino-acid region of influenza a virus PB1 protein is sufficient for complex formation with PA. J Virol 1995, 69: 6932-6939.PubMedPubMedCentral
66.
González S, Zürcher T, Ortin J: Identification of two separate domains in the influenza virus PB1 protein involved in the interaction with the PB2 and PA subunits: a model for viral RNA polymerase structure. Nucleic Acids Res 1996, 24: 4456-4463. 10.1093/nar/24.22.4456PubMedPubMedCentralCrossRef
67.
Perez DR, Donis RO: Functional analysis of PA binding by influenza a virus PB1: effects on polymerase activity and viral infectivity. J Virol 2001, 75: 8127-8136. 10.1128/JVI.75.17.8127-8136.2001PubMedPubMedCentralCrossRef
68.
He X, Zhou J, Bartlam M, Zhang R, Ma J, Lou Z, Li X, Li J, Joachimiak A, Zeng Z, Ge R, Rao Z, Liu Y: Crystal structure of the polymerase PA C -PB1 N complex from an avian influenza H5N1 virus. Nature 2008, 454: 1123-1126. 10.1038/nature07120PubMedCrossRef
69.
Sugiyama K, Obayashi E, Kawaguchi A, Suzuki Y, Tame JR, Nagata K, Park SY: Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase. EMBO J 2009, 28: 1803-1811. 10.1038/emboj.2009.138PubMedPubMedCentralCrossRef
70.
Krug RM, Aramini JM: Emerging antiviral targets for influenza A virus. Trends Pharmalcol Sci 2009, 30: 269-277. 10.1016/j.tips.2009.03.002CrossRef
71.
Wunderlich K, Mayer D, Ranadheera C, Holler AS, Mänz B, Martin A, Chase G, Tegge W, Frank R, Kessler U, Schwemmle M: Identification of a PA-binding peptide with inhibitory activity against influenza A and B virus replication. PLoS ONE 2009, 4: e7517. 10.1371/journal.pone.0007517PubMedPubMedCentralCrossRef
72.
Obayashi E, Yoshida H, Kawai F, Shibayama N, Kawaguchi A, Nagata K, Tame JR, Park SY: The structural basis for an essential subunit interaction in influenza virus RNA polymerase. Nature 2008, 454: 1127-1131. 10.1038/nature07225PubMedCrossRef
73.
Ghanem A, Mayer D, Chase G, Tegge W, Frank R, Kochs G, García-Sastre A, Schwemmel M: Peptide-mediated interference with influenza A virus polymerase. J Virol 2007, 81: 7801-7804. 10.1128/JVI.00724-07PubMedPubMedCentralCrossRef
74.
Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, Shiraki K: In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Ch 2002, 46: 977-981. 10.1128/AAC.46.4.977-981.2002CrossRef
75.
Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL: Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antivir Res 2013, 100: 446-454. 10.1016/j.antiviral.2013.09.015PubMedCrossRef
76.
Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Gunther S: Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antivir Res 2014, 105: 17-21.PubMedCrossRef
77.
Jin Z, Smith LK, Rajwanshi VK, Kim B, Deval J: The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) ribofuranosyl 5’-triphosphate towards influenza A virus polymerase. PloS ONE 2013, 8: e68347. 10.1371/journal.pone.0068347PubMedPubMedCentralCrossRef
78.
Sleeman K, Mishin VP, Deyde VM, Furuta Y, Klimov AI Gubareva LV: In vitro antiviral activity of favipiravir (T-705) against drug-resistant influenza and 2009 A (H1N1) viruses. Antimicrob. Agents Ch 2010, 54: 2517-2524. 10.1128/AAC.01739-09CrossRef
79.
Kiso M, Takahashi K, Sakai-Tagawa Y, Shinya K, Sakabe S, Le QM, Ozawa M, Furuta Y, Kawaoka Y: T-705 (favipiravir) activity against lethal H5N1 influenza A viruses. Proc Natl Acad Sci USA 2010, 107: 882-887. 10.1073/pnas.0909603107PubMedPubMedCentralCrossRef
80.
Takahashi K, Smee DF, Shiraki K, Kawaoka Y, Furuta Y: Pharmacological effects of favipiravir, an anti-influenza viral drug. J Med Pharm Sci 2011, 66: 429-441.
81.
Menéndez-Arias L, Álvarez M, Pacheco B: Nucleoside/nucleotide analog inhibitors of hepatitis B virus polymerase: mechanism of action and resistance. Curr Opin Virol 2014, 8: 1-9.PubMedCrossRef
82.
Amorim MJ, Kao RY, Digard P: Nucleozin Targets Cytoplasmic Trafficking of Viral Ribonucleoprotein-Rab11 Complexes in Influenza A Virus Infection. J Virol 2013, 87: 4694-4703. 10.1128/JVI.03123-12PubMedPubMedCentralCrossRef
83.
Su CY, Cheng TJ, Lin MI, Wang SY, Huang WI, Lin-Chu SY, Chen YH, Wu CY, Lai MM, Cheng WC, Wu YT, Tsai MD, Cheng YS, Wong CH: High-throughput identification of compounds targeting influenza RNA-dependent RNA polymerase activity. Proc Natl Acad Sci USA 2010, 107: 19151-19156. 10.1073/pnas.1013592107PubMedPubMedCentralCrossRef
84.
Gerritz SW, Cianci C, Kim S, Pearce BC, Meminie 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, Scartman R, Sinz M, Leyva-Grado VH, et al.: Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers. Proc Natl Acad Sci USA 2011, 108: 15366-15371. 10.1073/pnas.1107906108PubMedPubMedCentralCrossRef
85.
Cianci C, Gerritz SW, Deminie C, Krystal M: Influenza nucleoprotein: promising target for antiviral chemotherapy. Antiviral Chem Chemother 2013, 23: 77-91.CrossRef
86.
Perry NB, Blunt JW, Munro MH, Pannell LK: Mycalamide A, an antiviral compound from a New Zealand sponge of the genus Mycale. J Am Chem Soc 1988, 110: 4850-4851. 10.1021/ja00222a067CrossRef
87.
Hagiwara K, Kondoh Y, Ueda A, Yamada K, Goto H, Watanabe T, Nakata T, Osada H, Aida Y: Discovery of novel antiviral agents directed against the influenza A virus nucleoprotein using photo-cross-linked chemical arrays. Biochem Bioph Res Co 2010, 394: 721-727. 10.1016/j.bbrc.2010.03.058CrossRef
88.
Wang P, Palese P, O'Neill RE: The NPI-1/NPI-3 (karyopherin alpha) binding site on the influenza a virus nucleoprotein NP is a nonconventional nuclear localization signal. J Virol 1997, 71: 1850-1856.PubMedPubMedCentral
89.
Cros JF, García-Sastre A, Palese P: An unconventional NLS is critical for the nuclear import of the influenza A virus nucleoprotein and ribonucleoprotein. Traffic 2005, 6: 205-213. 10.1111/j.1600-0854.2005.00263.xPubMedCrossRef
90.
Momose F, Basler CF, O'Neill RE, Iwamatsu A, Palese P, Nagata K: Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis. J Virol 2001, 75: 1899-908. 10.1128/JVI.75.4.1899-1908.2001PubMedPubMedCentralCrossRef
91.
Wisskirchen C, Ludersdorfer TH, Müller DA, Moritz E, Pavlovic J: The cellular RNA helicase UAP56 is required for prevention of double-stranded RNA formation during influenza A virus infection. J Virol 2011, 85: 8646-8655. 10.1128/JVI.02559-10PubMedPubMedCentralCrossRef
92.
Kawaguchi A, Momose F, Nagata K: Replication-coupled and host factor-mediated encapsidation of the influenza virus genome by viral nucleoprotein. J Virol 2011, 85: 6197-6204. 10.1128/JVI.00277-11PubMedPubMedCentralCrossRef
93.
Lejal N, Tarus B, Bouguyon E, Chenevas S, Bertho N, Delmas B, Ruigrok RW, Di Primo C, Slama-Schwok A: Structure-based discovery of the novel antiviral properties of Naproxen against the nucleoprotein of influenza A virus. Antimicrob Agents Ch 2013, 57: 2231-2242. 10.1128/AAC.02335-12CrossRef
94.
Muratore G, Goracci L, Mercorelli B, Foeglein Á, Digard P, Cruciani G, Palù G, Loregian A: Small molecule inhibitors of influenza A and B viruses that act by disrupting subunit interactions of the viral polymerase. Proc Natl Acad Sci USA 2012, 109: 6247-6252. 10.1073/pnas.1119817109PubMedPubMedCentralCrossRef
95.
Fukuoka M, Minakuchi M, Kawaguchi A, Nagata K, Kamatari YO, Kuwata K: Structure-based discovery of anti-influenza virus A compounds among medicines. Biochim Biophys Acta 1820, 2012: 90-95.
96.
Li L, Chang SH, Xiang JF, Li Q, Liang HH, Tang YL, Liu YF: NMR identification of anti-influenza lead compound targeting at PA C subunit of H5N1 polymerase. Chinese Chem Lett 2012, 23: 89-92. 10.1016/j.cclet.2011.09.006CrossRef
97.
Shoji M, Takahashi E, Hatakeyama D, Iwai Y, Morita Y, Shirayama R, Echigo N, Kido H, Nakamura S, Mashino T, Okutani T, Kuzuhara T: Anti-influenza Activity of C 60 Fullerene Derivatives. PLoS ONE 2013, 8: e66337. 10.1371/journal.pone.0066337PubMedPubMedCentralCrossRef
98.
Pautus S, Sehr P, Lewis J, Fortuné A, Wolkerstorfer A, Szolar O, Guilligay D, Lunardi T, Décout J, Cusack S: New 7-Methylguanine Derivatives Targeting the Influenza Polymerase PB2 Cap-Binding Domain. J Med Chem 2013, 56: 8915-8930. 10.1021/jm401369yPubMedCrossRef
Metadata
Title
Emerging antiviral resistant strains of influenza A and the potential therapeutic targets within the viral ribonucleoprotein (vRNP) complex
Authors
Alicia M Davis
Bryan J Chabolla
Laura L Newcomb
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2014
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-11-167

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