Viral RNA polymerase: A promising antiviral target for influenza A virus

Current Medicinal Chemistry

Volumn 20, Issue 31, 2013, Pages 3923-3934

  Shi, Fangyuan ^a   Xie, Yuanchao ^a   Shi, Lifang ^b   Xu, Wenfang ^a  

^a SHANDONG UNIVERSITY   (China)

^b Affiliated Hospital of Logistics University of CAPF   (China)

Author keywords

Antiviral; Cap binding; Endonuclease; Influenza; Inhibitor; RNA polymerase

Indexed keywords

ANGELICIN; ANTIVIRUS AGENT; BENZBROMARONE; CELL DNA; DICLAZURIL; DOUBLE STRANDED RNA; ENDONUCLEASE; FAVIPIRAVIR; GLYCYRRHETINIC ACID; MESSENGER RNA; NUCLEOSIDE ANALOG; OLIGONUCLEOTIDE; OSELTAMIVIR; PERAMIVIR; PROTEIN M2; PURINE NUCLEOSIDE; RIBAVIRIN; RNA POLYMERASE; SHORT HAIRPIN RNA; SIALIDASE; SMALL INTERFERING RNA; VIRUS RNA; ZANAMIVIR;

ANTIGENIC VARIATION; ARTICLE; AVIAN INFLUENZA VIRUS; DRUG TARGETING; GENE FUNCTION; GENE SILENCING; HIGH THROUGHPUT SCREENING; HUMAN; IN VITRO STUDY; INFLUENZA A; INFLUENZA VACCINATION; INFLUENZA VIRUS A; INFLUENZA VIRUS A H5N1; LIFE CYCLE; NONHUMAN; RECOMBINANT PLASMID; RNA INTERFERENCE; VIRUS STRAIN; ZYGOTE;

ANIMALS; DNA-DIRECTED RNA POLYMERASES; ENZYME INHIBITORS; HUMANS; INFLUENZA A VIRUS; INFLUENZA, HUMAN; ORTHOMYXOVIRIDAE INFECTIONS; VIRAL PROTEINS;

EID: 84887900148     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/09298673113209990208     Document Type: Article

References (68)

1. Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza, A.V.; Abdel-Ghafar, A.N.; Chotpitayasunondh, T.; Gao, Z.; Hayden, F.G.; Nguyen, D.H.; de Jong, M.D.; Naghdaliyev, A.; Peiris, J.S.; Shindo, N.; Soeroso, S.; Uyeki, T.M., Update on avian influenza A (H5N1) virus infection in humans. N. Engl. J. Med., 2008, 358(3), 261-273.
2. Wright, P.F.; Webster, R.G. Orthomyxoviruses. Fields Virology, 2001, 1, 1533-1579.
3. Hay, A.J.; Wolstenholme, A.J.; Skehel, J.J.; Smith, M.H. The molecular basis of the specific anti-influenza action of amantadine. EMBO .J, 1985, 4(11), 3021-3024.
4. Mendel, D.B.; Tai, C.Y.; Escarpe, P.A.; Li, W.; Sidwell, R.W.; Huffman, J.H.; Sweet, C.; Jakeman, K.J.; Merson, J.; Lacy, S.A.; Lew, W.; Williams, M.A.; Zhang, L.; Chen, M.S.; Bischofberger, N.; Kim, C.U., Oral administration of a prodrug of the influenza virus neuraminidase inhibitor GS 4071 protects mice and ferrets against influenza infection. Antimicrob. Agents Chemother., 1998, 42(3), 640-646.
5. Deyde, V.M.; Xu, X.; Bright, R.A.; Shaw, M.; Smith, C.B.; Zhang, Y.; Shu, Y.; Gubareva, L.V.; Cox, N.J.; Klimov, A.I., Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. J. Infect. Dis., 2007, 196(2), 249-257.
6. de Jong, M.D.; Tran, T.T.; Truong, H.K.; Vo, M.H.; Smith, G.J.; Nguyen, V.C.; Bach, V.C.; Phan, T.Q.; Do, Q.H.; Guan, Y.; Peiris, J.S.; Tran, T.H.; Farrar, J. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N. Engl. J. Med., 2005, 353(25), 2667-2672.
7. Lackenby, A.; Hungnes, O.; Dudman, S.G.; Meijer, A.; Paget, W.J.; Hay, A.J.; Zambon, M.C. Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe. Euro Surveill., 2008, 13(5).
8. Xie, Y.; Gong, J.; Li, M.; Fang, H.; Xu, W. The medicinal potential of influenza virus surface proteins: hemagglutinin and neuraminidase. Curr. Med. Chem., 2011, 18(7), 1050-1066.
9. Noah, D.L.; Krug, R.M., Influenza virus virulence and its molecular determinants. Adv. Virus Res., 2005, 65, 121-145.
10. Wise, H.M.; Foeglein, A.; Sun, J.; Dalton, R.M.; Patel, S.; Howard, W.; Anderson, E.C.; Barclay, W.S.; Digard, P. A complicated message: Identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA. J. Virol., 2009, 83(16), 8021-8031.
11. McAuley, J.L.; Zhang, K.; McCullers, J.A. The effects of influenza A virus PB1-F2 protein on polymerase activity are strain specific and do not impact pathogenesis. J. Virol., 2010, 84(1), 558-564.
12. Skehel, J. An overview of influenza haemagglutinin and neuraminidase. Biologicals, 2009, 37(3), 177-178.
13. Portela, A.; Digard, P. The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J. Gen. Virol., 2002, 83(Pt 4), 723-734.
14. Iwatsuki-Horimoto, K.; Horimoto, T.; Fujii, Y.; Kawaoka, Y. Generation of influenza A virus NS2 (NEP) mutants with an altered nuclear export signal sequence. J. Virol., 2004, 78(18), 10149-10155.
15. Plotch, S.J.; Bouloy, M.; Ulmanen, I.; Krug, R.M. A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell, 1981, 23(3), 847-858.
16. Miotto, O.; Heiny, A.T.; Albrecht, R.; Garcia-Sastre, A.; Tan, T.W.; August, J.T.; Brusic, V. Complete-proteome mapping of human influenza A adaptive mutations: implications for human transmissibility of zoonotic strains. PLoS One, 2010, 5(2), e9025.
17. Ohtsu, Y.; Honda, Y.; Sakata, Y.; Kato, H.; Toyoda, T. Fine mapping of the subunit binding sites of influenza virus RNA polymerase. Microbiol. Immunol., 2002, 46(3), 167-175.
18. Hemerka, J.N.; Wang, D.; Weng, Y.; Lu, W.; Kaushik, R.S.; Jin, J.; Harmon, A.F.; Li, F. Detection and characterization of influenza A virus PA-PB2 interaction through a bimolecular fluorescence complementation assay. J. Virol., 2009, 83(8), 3944-3955.
19. 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(7208), 1123-1126.
20. Krug, R.M.; Aramini, J.M. Emerging antiviral targets for influenza A virus. Trends Pharmacol. Sci., 2009, 30(6), 269-277.
21. Poole, E.L.; Medcalf, L.; Elton, D.; Digard, P. Evidence that the Cterminal PB2-binding region of the influenza A virus PB1 protein is a discrete alpha-helical domain. FEBS Lett., 2007, 581(27), 5300-5306.
22. Nistal-Villan, E.; Garcia-Sastre, A. New prospects for the rational design of antivirals. Nat. Med., 2009, 15(11), 1253-1254.
23. Furuta, Y.; Takahashi, K.; Shiraki, K.; Sakamoto, K.; Smee, D.F.; Barnard, D.L.; Gowen, B.B.; Julander, J.G.; Morrey, J.D. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral. Res., 2009, 82(3), 95-102.
24. Newcomb, L.L.; Kuo, R.L.; Ye, Q.; Jiang, Y.; Tao, Y.J.; Krug, R.M. Interaction of the influenza a virus nucleocapsid protein with the viral RNA polymerase potentiates unprimed viral RNA replication. J. Virol., 2009, 83(1), 29-36.
25. Kashiwagi, T.; Hara, K.; Nakazono, Y.; Hamada, N.; Watanabe, H. Artificial hybrids of influenza A virus RNA polymerase reveal PA subunit modulates its thermal sensitivity. PLoS One, 2010, 5(12), e15140.
26. Hara, K.; Shiota, M.; Kido, H.; Ohtsu, Y.; Kashiwagi, T.; Iwahashi, J.; Hamada, N.; Mizoue, K.; Tsumura, N.; Kato, H.; Toyoda, T. Influenza virus RNA polymerase PA subunit is a novel serine protease with Ser624 at the active site. Genes Cells, 2001, 6(2), 87-97.
27. Dias, A.; Bouvier, D.; Crepin, T.; McCarthy, A.A.; Hart, D.J.; Baudin, F.; Cusack, S.; Ruigrok, R.W. The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature, 2009, 458(7240), 914-918.
28. Hara, K.; Schmidt, F.I.; Crow, M.; Brownlee, G.G. 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(16), 7789-7798.
29. Kashiwagi, T.; Leung, B.W.; Deng, T.; Chen, H.; Brownlee, G.G. The N-terminal region of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 (H5N1) influences promoter binding. PLoS One, 2009, 4(5), e5473.
30. 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. Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature, 2009, 458(7240), 909-913.
31. Doan, L.; Handa, B.; Roberts, N.A.; Klumpp, K. Metal ion catalysis of RNA cleavage by the influenza virus endonuclease. Biochemistry, 1999, 38(17), 5612-5619.
32. Suzuki, T.; Ainai, A.; Nagata, N.; Sata, T.; Sawa, H.; Hasegawa, H. A novel function of the N-terminal domain of PA in assembly of influenza A virus RNA polymerase. Biochem. Biophys. Res. Commun., 2011, 414(4), 719-726.
33. Neumann, G.; Brownlee, G.G.; Fodor, E.; Kawaoka, Y. Orthomyxovirus replication, transcription, and polyadenylation. Curr. Top. Microbiol. Immunol., 2004, 283, 121-143.
34. Guilligay, D.; Tarendeau, F.; Resa-Infante, P.; Coloma, R.; Crepin, T.; Sehr, P.; Lewis, J.; Ruigrok, R.W.; Ortin, J.; Hart, D.J.; Cusack, S. The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat. Struct. Mol. Biol., 2008, 15(5), 500-506.
35. Graef, K.M.; Vreede, F.T.; Lau, Y.F.; McCall, A.W.; Carr, S.M.; Subbarao, K.; Fodor, E. The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. J. Virol., 2010, 84(17), 8433-8445.
36. Hatta, M.; Gao, P.; Halfmann, P.; Kawaoka, Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science, 2001, 293(5536), 1840-1842.
37. Bradel-Tretheway, B.G.; Kelley, Z.; Chakraborty-Sett, S.; Takimoto, T.; Kim, B.; Dewhurst, S. The human H5N1 influenza A virus polymerase complex is active in vitro over a broad range of temperatures, in contrast to the WSN complex, and this property can be attributed to the PB2 subunit. J. Gen. Virol., 2008, 89(Pt 12), 2923-2932.
38. 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(11), 5398-5404.
39. Carr, S.M.; Carnero, E.; Garcia-Sastre, A.; Brownlee, G.G.; Fodor, E. Characterization of a mitochondrial-targeting signal in the PB2 protein of influenza viruses. Virology, 2006, 344(2), 492-508.
40. Wagner, C.R.; Iyer, V.V.; McIntee, E.J. Pronucleotides: toward the in vivo delivery of antiviral and anticancer nucleotides. Med. Res. Rev., 2000, 20(6), 417-451.
41. Tuttle, J.V.; Tisdale, M.; Krenitsky, T.A. Purine 2'-deoxy-2'- fluororibosides as antiinfluenza virus agents. J. Med. Chem., 1993, 36(1), 119-125.
42. Tisdale, M.; Ellis, M.; Klumpp, K.; Court, S.; Ford, M. Inhibition of influenza virus transcription by 2'-deoxy-2'-fluoroguanosine. Antimicrob. Agents Chemother., 1995, 39(11), 2454-2458.
43. Furuta, Y.; Takahashi, K.; Fukuda, Y.; Kuno, M.; Kamiyama, T.; Kozaki, K.; Nomura, N.; Egawa, H.; Minami, S.; Watanabe, Y.; Narita, H.; Shiraki, K. In vitro and in vivo activities of antiinfluenza virus compound T-705. Antimicrob. Agents Chemother., 2002, 46(4), 977-981.
44. Furuta, Y.; Takahashi, K.; Kuno-Maekawa, M.; Sangawa, H.; Uehara, S.; Kozaki, K.; Nomura, N.; Egawa, H.; Shiraki, K. Mechanism of action of T-705 against influenza virus. Antimicrob. Agents Chemother., 2005, 49(3), 981-986.
45. Smee, D.F.; Hurst, B.L.; Wong, M.H.; Bailey, K.W.; Tarbet, E.B.; Morrey, J.D.; Furuta, Y. Effects of the combination of favipiravir (T-705) and oseltamivir on influenza A virus infections in mice. Antimicrob. Agents Chemother., 2010, 54(1), 126-133.
46. Tarbet, E.B.; Maekawa, M.; Furuta, Y.; Babu, Y.S.; Morrey, J.D.; Smee, D.F. Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009 (H1N1) virus infections in mice. Antiviral. Res., 2012, 94(1), 103-110.
47. Jones, R.J.; Bischofberger, N. Minireview: nucleotide prodrugs. Antiviral. Res., 1995, 27(1-2), 1-17.
48. Hecker, S.J.; Erion, M.D., Prodrugs of phosphates and phosphonates. J. Med. Chem., 2008, 51(8), 2328-2345.
49. Meneghesso, S.; Vanderlinden, E.; Stevaert, A.; McGuigan, C.; Balzarini, J.; Naesens, L. Synthesis and biological evaluation of pyrimidine nucleoside monophosphate prodrugs targeted against influenza virus. Antiviral. Res., 2012, 94(1), 35-43.
50. Iwai, Y.; Takahashi, H.; Hatakeyama, D.; Motoshima, K.; Ishikawa, M.; Sugita, K.; Hashimoto, Y.; Harada, Y.; Itamura, S.; Odagiri, T.; Tashiro, M.; Sei, Y.; Yamaguchi, K.; Kuzuhara, T. Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide. Bioorg. Med. Chem., 2010, 18(14), 5379-5390.
51. Yamada, K.; Koyama, H.; Hagiwara, K.; Ueda, A.; Sasaki, Y.; Kanesashi, S.N.; Ueno, R.; Nakamura, H.K.; Kuwata, K.; Shimizu, K.; Suzuki, M.; Aida, Y. Identification of a novel compound with antiviral activity against influenza A virus depending on PA subunit of viral RNA polymerase. Microbes. Infect., 2012.
52. ElHefnawi, M.; Alaidi, O.; Mohamed, N.; Kamar, M.; El-Azab, I.; Zada, S.; Siam, R. Identification of novel conserved functional motifs across most Influenza A viral strains. Virol. J., 2011, 8, 44.
53. Fukuoka, M.; Minakuchi, M.; Kawaguchi, A.; Nagata, K.; Kamatari, Y.O.; Kuwata, K. Structure-based discovery of antiinfluenza virus A compounds among medicines. Biochim. Biophys. Acta, 2012, 1820(2), 90-95.
54. Li, L.; Chang, S.H.; Xiang, J.F.; Li, Q.; Liang, H.H.; Tang, Y.L.; Liu, Y.F. NMR identification of anti-influenza lead compound. Chinese Chem. Lett., 2011.
55. Kim, J.; Lee, C.; Chong, Y. Identification of potential influenza virus endonuclease inhibitors through virtual screening based on the 3D-QSAR model. SAR QSAR Environ. Res., 2009, 20(1-2), 103-118.
56. Tomassini, J.; Selnick, H.; Davies, M.E.; Armstrong, M.E.; Baldwin, J.; Bourgeois, M.; Hastings, J.; Hazuda, D.; Lewis, J.; McClements, W.; et al., Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds. Antimicrob. Agents Chemother., 1994, 38(12), 2827-2837.
57. Tomassini, J.E.; Davies, M.E.; Hastings, J.C.; Lingham, R.; Mojena, M.; Raghoobar, S.L.; Singh, S.B.; Tkacz, J.S.; Goetz, M.A. A novel antiviral agent which inhibits the endonuclease of influenza viruses. Antimicrob. Agents Chemother., 1996, 40(5), 1189-1193.
58. Singh, S.B.; Tomassini, J.E. Synthesis of natural flutimide and analogous fully substituted pyrazine-2,6-diones, endonuclease inhibitors of influenza virus. J. Org. Chem., 2001, 66(16), 5504-5516.
59. Parkes, K.E.; Ermert, P.; Fassler, J.; Ives, J.; Martin, J.A.; Merrett, J.H.; Obrecht, D.; Williams, G.; Klumpp, K. Use of a pharmacophore model to discover a new class of influenza endonuclease inhibitors. J. Med. Chem., 2003, 46(7), 1153-1164.
60. Lu, F.J.; Tseng, S.N.; Li, M.L.; Shih, S.R. In vitro anti-influenza virus activity of synthetic humate analogues derived from protocatechuic acid. Arch. Virol., 2002, 147(2), 273-284.
61. Ghanem, A.; Mayer, D.; Chase, G.; Tegge, W.; Frank, R.; Kochs, G.; Garcia-Sastre, A.; Schwemmle, M. Peptide-mediated interference with influenza A virus polymerase. J. Virol., 2007, 81(14), 7801-7804.
62. Muratore, G.; Goracci, L.; Mercorelli, B.; Foeglein, A.; Digard, P.; Cruciani, G.; Palu, 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. U S A, 2012, 109(16), 6247-6252.
63. Yeh, J.Y.; Coumar, M.S.; Horng, J.T.; Shiao, H.Y.; Kuo, F.M.; Lee, H.L.; Chen, I.C.; Chang, C.W.; Tang, W.F.; Tseng, S.N.; Chen, C.J.; Shih, S.R.; Hsu, J.T.; Liao, C.C.; Chao, Y.S.; Hsieh, H.P. Anti-influenza drug discovery: structure-activity relationship and mechanistic insight into novel angelicin derivatives. J. Med. Chem., 2010, 53(4), 1519-1533.
64. Su, C.Y.; Cheng, T.J.; Lin, M.I.; Wang, S.Y.; Huang, W.I.; Lin-Chu, S.Y.; Chen, Y.H.; Wu, C.Y.; Lai, M.M.; Cheng, W.C.; Wu, Y.T.; Tsai, M.D.; Cheng, Y.S.; Wong, C.H. High-throughput identification of compounds targeting influenza RNA-dependent RNA polymerase activity. Proc. Natl. Acad. Sci. U S A, 2010, 107(45), 19151-19156.
65. Kim, D.; Rossi, J. RNAi mechanisms and applications. Biotechniques, 2008, 44(5), 613-616.
66. Grimm, D.; Kay, M.A. Combinatorial RNAi: a winning strategy for the race against evolving targets? Mol. Ther., 2007, 15(5), 878-888.
67. Li, W.; Yang, X.; Jiang, Y.; Wang, B.; Yang, Y.; Jiang, Z.; Li, M. Inhibition of influenza A virus replication by RNA interference targeted against the PB1 subunit of the RNA polymerase gene. Arch. Virol., 2011, 156(11), 1979-1987.
68. Zhang, W.; Wang, C.Y.; Yang, S.T.; Qin, C.; Hu, J.L.; Xia, X.Z. Inhibition of highly pathogenic avian influenza virus H5N1 replication by the small interfering RNA targeting polymerase A gene. Biochem. Biophys. Res. Commun., 2009, 390(3), 421-426.