A novel small-molecule inhibitor of influenza A virus acts by suppressing PA endonuclease activity of the viral polymerase

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Yuan, Shuofeng ^a   Chu, Hin ^a   Singh, Kailash ^a   Zhao, Hanjun ^a   Zhang, Ke ^a   Kao, Richard Y T ^a   Chow, Billy K C ^a   Zhou, Jie ^a   Zheng, Bo Jian ^a  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; PA PROTEIN, INFLUENZA VIRUSES; RNA DIRECTED RNA POLYMERASE; VIRAL PROTEIN;

ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; DRUG EFFECTS; DRUG POTENTIATION; ENZYMOLOGY; FEMALE; INFLUENZA A VIRUS; INTRANASAL DRUG ADMINISTRATION; ISOLATION AND PURIFICATION; LUNG; ORTHOMYXOVIRIDAE INFECTIONS; PATHOLOGY; PHYSIOLOGY; PRECLINICAL STUDY; SURVIVAL ANALYSIS; TREATMENT OUTCOME; VIROLOGY; VIRUS LOAD; VIRUS REPLICATION;

ADMINISTRATION, INTRANASAL; ANIMALS; ANTIVIRAL AGENTS; DRUG EVALUATION, PRECLINICAL; DRUG SYNERGISM; FEMALE; INFLUENZA A VIRUS; LUNG; MICE, INBRED BALB C; ORTHOMYXOVIRIDAE INFECTIONS; RNA REPLICASE; SURVIVAL ANALYSIS; TREATMENT OUTCOME; VIRAL LOAD; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 84960487693     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep22880     Document Type: Article

References (60)

1. Novel Swine-Origin Influenza A. V. I. T., et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360, 2605-2615 (2009
2. Gao R., et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368, 1888-1897 (2013
3. Peiris J. S., de Jong M. D., & Guan Y. Avian influenza virus (H5N1): a threat to human health. Clin Microbiol Rev 20, 243-267 (2007
4. Monto A. S. Vaccines and antiviral drugs in pandemic preparedness. Emerg Infect Dis 12, 55-60 (2006
5. Bright R. A., Shay D. K., Shu B., Cox N. J., & Klimov A. I. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA 295, 891-894 (2006
6. Hai R., et al. Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility. Nat Commun 4, 2854 (2013
7. Thorlund K., Awad T., Boivin G., & Thabane L. Systematic review of influenza resistance to the neuraminidase inhibitors. BMC Infect Dis 11, 134 (2011
8. Das K., Aramini J. M., Ma L.-C., Krug R. M., & Arnold E. Structures of influenza A proteins and insights into antiviral drug targets. Nat Struct Mol Biol 17, 530-538 (2010
9. Kumar N., Sharma N. R., Ly H., Parslow T. G., & Liang Y. Receptor tyrosine kinase inhibitors that block replication of influenza a and other viruses. Antimicrob Agents Chemother 55, 5553-5559 (2011
10. Reich S., et al. Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature 516, 361-366 (2014
11. Boivin S., Cusack S., Ruigrok R. W., & Hart D. J. Influenza A virus polymerase: structural insights into replication and host adaptation mechanisms. J Biol Chem 285, 28411-28417 (2010
12. Dias A., et al. The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458, 914-918 (2009
13. Yuan P. W., et al. Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature 458, 909-912 (2009
14. Stevaert A., et al. Mutational analysis of the binding pockets of the diketo acid inhibitor L-742,001 in the influenza virus PA endonuclease. J Virol 87, 10524-10538 (2013
15. Pinilla L. T., Holder B. P., Abed Y., Boivin G., & Beauchemin C. A. The H275Y neuraminidase mutation of the pandemic A/H1N1 influenza virus lengthens the eclipse phase and reduces viral output of infected cells, potentially compromising fitness in ferrets. J Virol 86, 10651-10660 (2012
16. Uemura Y., et al. The N-terminal fragment of PA subunit of the influenza A virus effectively inhibits ribonucleoprotein (RNP) activity via suppression of its RNP expression. J Infect Chemother 21, 296-301 (2015
17. DuBois R. M., et al. Structural and biochemical basis for development of influenza virus inhibitors targeting the PA endonuclease. PLoS Pathog 8, e1002830 (2012
18. Kowalinski E., et al. Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase. PLoS Pathog 8, e1002831 (2012
19. Hastings J. C., Selnick H., Wolanski B., & Tomassini J. E. Anti-influenza virus activities of 4-substituted 2,4-dioxobutanoic acid inhibitors. Antimicrob Agents Chemother 40, 1304-1307 (1996
20. Tomassini J., et al. Inhibition of cap (m7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds. Antimicrob Agents Chemother 38, 2827-2837 (1994
21. Singh S. B. Total synthesis of flutimide, a novel endonuclease inhibitor of influenza virus. Tetrahedron Letters 36, 2009-2012 (1995
22. Sagong H. Y., et al. 3-Hydroxyquinolin-2(1H)-ones As Inhibitors of Influenza A Endonuclease. ACS Med Chem Lett 4, 547-550 (2013
23. Sagong H. Y., et al. Phenyl substituted 4-hydroxypyridazin-3(2H)-ones and 5-hydroxypyrimidin-4(3H)-ones: inhibitors of influenza A endonuclease. J Med Chem 57, 8086-8098 (2014
24. Parkes K. E., et al. Use of a pharmacophore model to discover a new class of influenza endonuclease inhibitors. J Med Chem 46, 1153-1164 (2003
25. Carcelli M., et al. Metal-chelating 2-hydroxyphenyl amide pharmacophore for inhibition of influenza virus endonuclease. Mol Pharm 11, 304-316 (2014
26. Yan Z., Zhang L., Fu H., Wang Z., & Lin J. Design of the influenza virus inhibitors targeting the PA endonuclease using 3D-QSAR modeling, side-chain hopping, and docking. Bioorg Med Chem Lett 24, 539-547 (2014
27. 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 20, 103-118 (2009
28. Shoji M., et al. Anti-influenza activity of c60 fullerene derivatives. PLoS One 8, e66337 (2013
29. Noble E., Cox A., Deval J., & Kim B. Endonuclease substrate selectivity characterized with full-length PA of influenza A virus polymerase. Virology 433, 27-34 (2012
30. Shibagaki Y., et al. An efficient screening system for influenza virus cap-dependent endonuclease inhibitors. J Virol Methods 202, 8-14 (2014
31. Baughman B. M., et al. Identification of influenza endonuclease inhibitors using a novel fluorescence polarization assay. ACS Chem Biol 7, 526-534 (2012
32. Sinha C., et al. Forster resonance energy transfer?an approach to visualize the spatiotemporal regulation of macromolecular complex formation and compartmentalized cell signaling. Biochim Biophys Acta 1840, 3067-3072 (2014
33. Madiraju C., et al. TR-FRET-based high-throughput screening assay for identification of UBC13 inhibitors. J Biomol Screen 17, 163-176 (2012
34. Song Y., & Liao J. An in vitro Forster resonance energy transfer-based high-throughput screening assay for inhibitors of proteinprotein interactions in SUMOylation pathway. Assay Drug Dev Technol 10, 336-343 (2012
35. Kao R. Y., et al. Identification of influenza A nucleoprotein as an antiviral target. Nat Biotechnol 28, 600-605 (2010
36. Tomassini J. E., et al. A novel antiviral agent which inhibits the endonuclease of influenza viruses. Antimicrob Agents Chemother 40, 1189-1193 (1996
37. Lipinski C. A. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 1, 337-341 (2004
38. Eisfeld A. J., Neumann G., & Kawaoka Y. At the centre: influenza A virus ribonucleoproteins. Nat Rev Microbiol 13, 28-41 (2015
39. Huggins J. W., Robins R. K., & Canonico P. G. Synergistic antiviral effects of ribavirin and the C-nucleoside analogs tiazofurin and selenazofurin against togaviruses, bunyaviruses, and arenaviruses. Antimicrob Agents Chemother 26, 476-480 (1984
40. Meletiadis J., Pournaras S., Roilides E., & Walsh T. J. Defining fractional inhibitory concentration index cutoffs for additive interactions based on self-drug additive combinations, Monte Carlo simulation analysis, and in vitro-in vivo correlation data for antifungal drug combinations against Aspergillus fumigatus. Antimicrob Agents Chemother 54, 602-609 (2010
41. Berenbaum M. C. What is synergy? Pharmacol Rev 41, 93-141 (1989
42. Palmier M. O., & Van Doren S. R. Rapid determination of enzyme kinetics from fluorescence: overcoming the inner filter effect. Anal Biochem 371, 43-51 (2007
43. Taylor R. M. Experimental Infection with Influenza a Virus in Mice: The Increase in Intrapulmonary Virus after Inoculation and the Influence of Various Factors Thereon. J Exp Med 73, 43-55 (1941
44. Smee D. F., von Itzstein M., Bhatt B., & Tarbet E. B. Exacerbation of influenza virus infections in mice by intranasal treatments and implications for evaluation of antiviral drugs. Antimicrob Agents Chemother 56, 6328-6333 (2012
45. Judd A. K., et al. In vivo anti-influenza virus activity of a zinc finger peptide. Antimicrob Agents Chemother 41, 687-692 (1997
46. Fudo S., et al. Structural and computational study on inhibitory compounds for endonuclease activity of influenza virus polymerase. Bioorg Med Chem 23, 5466-5475 (2015
47. Neumann G., Brownlee G. G., Fodor E., & Kawaoka Y. Orthomyxovirus replication, transcription, and polyadenylation. Curr Top Microbiol Immunol 283, 121-143 (2004
48. Hay A. J., Lomniczi B., Bellamy A. R., & Skehel J. J. Transcription of the influenza virus genome. Virology 83, 337-355 (1977
49. Crepin T., et al. Mutational and metal binding analysis of the endonuclease domain of the influenza virus polymerase PA subunit. J Virol 84, 9096-9104 (2010
50. Guilligay D., et al. The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat Struct Mol Biol 15, 500-506 (2008
51. Massari S., et al. A Broad Anti-influenza Hybrid Small Molecule That Potently Disrupts the Interaction of Polymerase Acidic Protein-Basic Protein 1 (PA-PB1) Subunits. J Med Chem 58, 3830-3842 (2015
52. Govorkova E. A., Fang H. B., Tan M., & Webster R. G. Neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in MDCK cells. Antimicrob Agents Chemother 48, 4855-4863 (2004
53. Ilyushina N. A., et al. Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice. Antimicrob Agents Chemother 52, 3889-3897 (2008
54. Hurt A. C., Holien J. K., Parker M., Kelso A., & Barr I. G. Zanamivir-resistant influenza viruses with a novel neuraminidase mutation. J Virol 83, 10366-10373 (2009
55. Zheng B. J., et al. 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, 8091-8096 (2008
56. Yuan S., et al. Cross-protection of influenza A virus infection by a DNA aptamer targeting the PA endonuclease domain. Antimicrob Agents Chemother 59, 4082-4093 (2015
57. Odds F. C. Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 52, 1 (2003
58. Watanabe T., et al. Characterization of H7N9 influenza A viruses isolated from humans. Nature 501, 551-555 (2013
59. Hoffmann E., Stech J., Guan Y., Webster R. G., & Perez D. R. Universal primer set for the full-length amplification of all influenza A viruses. Arch Virol 146, 2275-2289 (2001
60. Ng A. K., et al. Influenza polymerase activity correlates with the strength of interaction between nucleoprotein and PB2 through the host-specific residue K/E627. PLoS One 7, e36415 (2012