Peptidomimetic furin inhibitor MI-701 in combination with oseltamivir and ribavirin efficiently blocks propagation of highly pathogenic avian influenza viruses and delays high level oseltamivir resistance in MDCK cells

Antiviral Research

Volumn 120, Issue 1, 2015, Pages 89-100

  Lu, Yinghui ^a   Hardes, Kornelia ^a   Dahms, Sven O ^b   Böttcher Friebertshäuser, Eva ^a   Steinmetzer, Torsten ^a   Than, Manuel E ^b   Klenk, Hans Dieter ^a   Garten, Wolfgang ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b FRITZ LIPMANN INSTITUTE   (Germany)

Author keywords

Combinatorial drug treatment; Delayed resistance; Peptidomimetic furin inhibitor

Indexed keywords

ANTIVIRUS AGENT; ENZYME INHIBITOR; FURIN; MI 701; OSELTAMIVIR; PEPTIDOMIMETIC AGENT; RIBAVIRIN; UNCLASSIFIED DRUG; VIRUS ENZYME; VIRUS RNA; MUTANT PROTEIN; NA PROTEIN, INFLUENZA A VIRUS; SIALIDASE; VIRAL PROTEIN;

ANIMAL CELL; ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ARTICLE; AVIAN INFLUENZA; AVIAN INFLUENZA VIRUS; CELL CULTURE; DRUG EFFICACY; DRUG POTENTIATION; EC50; IN VITRO STUDY; INFLUENZA VIRUS A; MDCK CELL LINE; MOLECULAR MODEL; NONHUMAN; PRIORITY JOURNAL; VIROGENESIS; VIRUS ATTACHMENT; VIRUS MUTATION; VIRUS REPLICATION; VIRUS STRAIN; VIRUS TITRATION; ANIMAL; ANTAGONISTS AND INHIBITORS; DOG; DRUG EFFECTS; GENETICS; GROWTH, DEVELOPMENT AND AGING; INFLUENZA A VIRUS (H5N1); INFLUENZA A VIRUS (H7N1); METABOLISM; MICROBIAL SENSITIVITY TEST; MISSENSE MUTATION;

AVIAN INFLUENZA VIRUS;

ANIMALS; ANTIVIRAL AGENTS; DOGS; DRUG RESISTANCE, VIRAL; DRUG SYNERGISM; FURIN; INFLUENZA A VIRUS, H5N1 SUBTYPE; INFLUENZA A VIRUS, H7N1 SUBTYPE; MADIN DARBY CANINE KIDNEY CELLS; MICROBIAL SENSITIVITY TESTS; MUTANT PROTEINS; MUTATION, MISSENSE; NEURAMINIDASE; OSELTAMIVIR; PEPTIDOMIMETICS; RIBAVIRIN; VIRAL PROTEINS;

EID: 84934890156     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2015.05.006     Document Type: Article

References (78)

1. Ascierto, P.A., Marincola, F.M., 2011. Combination therapy: the next opportunity and challenge of medicine. J. Transl. Med. 9, 115.
2. Basak, A., Chen, A., Scamuffa, N., Mohottalage, D., Basak, S., Khatib, A.M., 2010. Blockade of furin activity and furin-induced tumor cells malignant phenotypes by the chemically synthesized human furin prodomain. Curr. Med. Chem. 17, 2214-2221.
3. Baz, M., Luke, C.J., Cheng, X., Jin, H., Subbarao, K., 2013. H5N1 vaccines in humans. Virus Res. 178, 78-98.
4. Becker, G.L., Hardes, K., Steinmetzer, T., 2011. New substrate analogue furin inhibitors derived from 4-amidinobenzylamide. Bioorg. Med. Chem. Lett. 21, 4695-4697.
5. Becker, G.L., Lu, Y., Hardes, K., Strehlow, B., Levesque, C., Lindberg, I., Sandvig, K., Bakowsky, U., Day, R., Garten, W., Steinmetzer, T., 2012. Highly potent inhibitors of proprotein convertase furin as potential drugs for treatment of infectious diseases. J. Biol. Chem. 287, 21992-22003.
6. Becker, G.L., Sielaff, F., Than, M.E., Lindberg, I., Routhier, S., Day, R., Lu, Y., Garten, W., Steinmetzer, T., 2010. Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics. J. Med. Chem. 53, 1067-1075.
7. Beigel, J., Bray, M., 2008. Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 78, 91-102.
8. Böttcher-Friebertshäuser, E., Freuer, C., Sielaff, F., Schmidt, S., Eickmann, M., Uhlendorff, J., Steinmetzer, T., Klenk, H.D., Garten, W., 2010. Cleavage of influenza virus hemagglutinin by airway proteases TMPRSS2 and HAT differs in subcellular localization and susceptibility to protease inhibitors. J. Virol. 84, 5605-5614.
9. Böttcher-Friebertshäuser, E., Garten, W., Matrosovich, M., Klenk, H.D., 2014. The hemagglutinin: a determinant of pathogenicity. Curr. Top. Microbiol. Immunol. 385, 3-34.
10. Böttcher-Friebertshäuser, E., Garten, W., Matrosovich, M., Klenk, H.D., 2014. The hemagglutinin: a determinant of pathogenicity. Curr. Top. Microbiol. Immunol. 385, 3-34.
11. Böttcher-Friebertshäuser, E., Lu, Y., Meyer, D., Sielaff, F., Steinmetzer, T., Klenk, H.D., Garten, W., 2012. Hemagglutinin activating host cell proteases provide promising drug targets for the treatment of influenza A and B virus infections. Vaccine 30, 7374-7380.
12. Bray, M., 2008. Highly pathogenic RNA viral infections: challenges for antiviral research. Antiviral Res. 78, 1-8.
13. Brünger, A.T., 2007. Version 1.2 of the Crystallography and NMR system. Nat. Protoc. 2, 2728-2733.
14. Capua, I., Alexander, D.J., 2007. Animal and human health implications of avian influenza infections. Biosci. Rep. 27, 359-372.
15. Cheung, C.L., Rayner, J.M., Smith, G.J., Wang, P., Naipospos, T.S., Zhang, J., Yuen, K.Y., Webster, R.G., Peiris, J.S., Guan, Y., Chen, H., 2006. Distribution of amantadineresistant H5N1 avian influenza variants in Asia. J. Infect. Dis. 193, 1626-1629.
16. Dahms, S.O., Hardes, K., Becker, G.L., Steinmetzer, T., Brandstetter, H., Than, M.E., 2014. X-ray structures of human furin in complex with competitive inhibitors. ACS Chem. Biol. 9, 1113-1118.
17. De Clercq, E., 2013. Dancing with chemical formulae of antivirals: a panoramic view (Part 2). Biochem. Pharmacol. 86, 1397-1410.
18. De Clercq, E., Neyts, J., 2007. Avian influenza A (H5N1) infection: targets and strategies for chemotherapeutic intervention. Trends Pharmacol. Sci. 28, 280-285.
19. 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., 2005. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N. Engl. J. Med. 353, 2667-2672.
20. Deryabin, P.G., Galegov, G.A., Konstantinova, I.D., Muzyka, I.S., Miroshnikov, A.I., D L'Vov, K., 2014. The combination of ribavirin and ozeltamivir effectively inhibits reproduction of influenza A virus resistant to rimantadine (amantadine) in vitro and in vivo. Dokl. Biochem. Biophys. 455, 80-83.
21. Dunning, J., Baillie, J.K., Cao, B., Hayden, F.G., 2014. Antiviral combinations for severe influenza. Lancet Infect. Dis. 14, 1259-1270.
22. Emsley, P., Lohkamp, B., Scott, W.G., Cowtan, K., 2010. Features and development of Coot. Acta Crystallogr. Sect. D: Biol. Crystallogr. 66, 486-501.
23. Feeney, E.R., Chung, R.T., 2014. Antiviral treatment of hepatitis C. BMJ 348, g3308.
24. Gagnon, H., Beauchemin, S., Kwiatkowska, A., Couture, F., D'Anjou, F., Levesque, C., Dufour, F., Desbiens, A.R., Vaillancourt, R., Bernard, S., Desjardins, R., Malouin, F., Dory, Y.L., Day, R., 2014. Optimization of furin inhibitors to protect against the activation of influenza hemagglutinin H5 and Shiga toxin. J. Med. Chem. 57, 29-41.
25. Gambotto, A., Barratt-Boyes, S.M., de Jong, M.D., Neumann, G., Kawaoka, Y., 2008. Human infection with highly pathogenic H5N1 influenza virus. Lancet 371, 1464-1475.
26. Garred, O., van Deurs, B., Sandvig, K., 1995. Furin-induced cleavage and activation of Shiga toxin. J. Biol. Chem. 270, 10817-10821.
27. Garten, W., Hallenberger, S., Ortmann, D., Schäfer, W., Vey, M., Angliker, H., Shaw, E., Klenk, H.D., 1994. Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones. Biochimie 76, 217-225.
28. Garten, W., Klenk, H.D., 2008. Cleavage activation of the influenza virus hemagglutinin and its role in pathogenesis. In: Klenk, H.D., Matrosovich, M., Stech, J. (Eds.), Avian Influenza. Karger, Basel, pp. 156-167.
29. Gordon, V.M., Klimpel, K.R., Arora, N., Henderson, M.A., Leppla, S.H., 1995. Proteolytic activation of bacterial toxins by eukaryotic cells is performed by furin and by additional cellular proteases. Infect. Immun. 63, 82-87.
30. Hallenberger, S., Bosch, V., Angliker, H., Shaw, E., Klenk, H.D., Garten, W., 1992. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature 360, 358-361.
31. Horimoto, T., Kawaoka, Y., 1994. Reverse genetics provides direct evidence for a correlation of hemagglutinin cleavability and virulence of an avian influenza A virus. J. Virol. 68, 3120-3128.
32. Hui, D.S., Lee, N., Chan, P.K., 2013. Adjunctive therapies and immunomodulatory agents in the management of severe influenza. Antiviral Res. 98, 410-416.
33. Hurt, A.C., 2014. The epidemiology and spread of drug resistant human influenza viruses. Current opinion in virology 8, 22-29.
34. Ilyushina, N.A., Bovin, N.V., Webster, R.G., Govorkova, E.A., 2006. Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res. 70, 121-131.
35. Imai, M., Watanabe, T., Hatta, M., Das, S.C., Ozawa, M., Shinya, K., Zhong, G., Hanson, A., Katsura, H., Watanabe, S., Li, C., Kawakami, E., Yamada, S., Kiso, M., Suzuki, Y., Maher, E.A., Neumann, G., Kawaoka, Y., 2012. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486, 420-428.
36. Kacprzak, M.M., Peinado, J.R., Than, M.E., Appel, J., Henrich, S., Lipkind, G., Houghten, R.A., Bode, W., Lindberg, I., 2004. Inhibition of furin by polyarginine-containing peptides: nanomolar inhibition by nona-D-arginine. J. Biol. Chem. 279, 36788-36794.
37. Klenk, H.D., Garten, W., 1994. Activation cleavage of viral spike proteins. In: Wimmer, E. (Ed.), Cellular Receptors for Animal Viruses. Monograph 28. Gold Spring Harbor Laboratory Press, pp. 241-280.
38. Klenk, H.D., Rott, R., Orlich, M., Blödorn, J., 1975. Activation of influenza A viruses by trypsin treatment. Virology 68, 426-439.
39. Krammer, F., Hai, R., Yondola, M., Tan, G.S., Leyva-Grado, V.H., Ryder, A.B., Miller, M.S., Rose, J.K., Palese, P., Garcia-Sastre, A., Albrecht, R.A., 2014. Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets. J. Virol. 88, 3432-3442.
40. Linster, M., van Boheemen, S., de Graaf, M., Schrauwen, E.J., Lexmond, P., Manz, B., Bestebroer, T.M., Baumann, J., van Riel, D., Rimmelzwaan, G.F., Osterhaus, A.D., Matrosovich, M., Fouchier, R.A., Herfst, S., 2014. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell 157, 329-339.
41. Liu, Q., Liu, D.Y., Yang, Z.Q., 2013. Characteristics of human infection with avian influenza viruses and development of new antiviral agents. Acta Pharmacol. Sin. 34, 1257-1269.
42. Lowen, A.C., Palese, P., 2007. Influenza virus transmission: basic science and implications for the use of antiviral drugs during a pandemic. Infect. Disord. Drug Targets 7, 318-328.
43. Ludwig, S., Zell, R., Schwemmle, M., Herold, S., 2014. Influenza, a One Health paradigm - novel therapeutic strategies to fight a zoonotic pathogen with pandemic potential. Int. J. Med. Microbiol. 304, 894-901.
44. Lupiani, B., Reddy, S.M., 2009. The history of avian influenza. Comp. Immunol. Microbiol. Infect. Dis. 32, 311-323.
45. Marathe, B.M., Léveque, V., Klumpp, K., Webster, R.G., Govorkova, E.A., 2013. Determination of neuraminidase kinetic constants using whole influenza virus preparations and correction for spectroscopic interference by a fluorogenic substrate. PLoS One 8, e71401.
46. Matrosovich, M., Matrosovich, T., Garten, W., Klenk, H.D., 2006. New low-viscosity overlay medium for viral plaque assays. Virol. J. 3, 63.
47. Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55-63.
48. Nguyen, J.T., Hoopes, J.D., Smee, D.F., Prichard, M.N., Driebe, E.M., Engelthaler, D.M., Le, M.H., Keim, P.S., Spence, R.P., Went, G.T., 2009. Triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro. Antimicrob. Agents Chemother. 53, 4115-4126.
49. Nguyen, J.T., Smee, D.F., Barnard, D.L., Julander, J.G., Gross, M., de Jong, M.D., Went, G.T., 2012. Efficacy of combined therapy with amantadine, oseltamivir, and ribavirin in vivo against susceptible and amantadine-resistant influenza A viruses. PLoS One 7, e31006.
50. Ozden, S., Lucas-Hourani, M., Ceccaldi, P.E., Basak, A., Valentine, M., Benjannet, S., Hamelin, J., Jacob, Y., Mamchaoui, K., Mouly, V., Desprès, P., Gessain, A., Butler-Browne, G., Chrétien, M., Tangy, F., Vidalain, P.O., Seidah, N.G., 2008. Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein. J. Biol. Chem. 283, 21899-21908.
51. Pasquato, A., Ramos da Palma, J., Galan, C., Seidah, N.G., Kunz, S., 2013. Viral envelope glycoprotein processing by proprotein convertases. Antiviral Res. 99, 49-60.
52. Perez, D.R., Garcia-Sastre, A., 2013. H5N1, a wealth of knowledge to improve pandemic preparedness. Virus Res. 178, 1-2.
53. Pierson, T.C., Diamond, M.S., 2012. Degrees of maturity: the complex structure and biology of flaviviruses. Curr. Opin. Virol. 2, 168-175.
54. Pirrone, V., Thakkar, N., Jacobson, J.M., Wigdahl, B., Krebs, F.C., 2011. Combinatorial approaches to the prevention and treatment of HIV-1 infection. Antimicrob. Agents Chemother. 55, 1831-1842.
55. Planz, O., 2013. Development of cellular signaling pathway inhibitors as new antivirals against influenza. Antiviral Res. 98, 457-468.
56. Potier, M., Mameli, L., Belisle, M., Dallaire, L., Melancon, S.B., 1979. Fluorometric assay of neuraminidase with a sodium (4-methylumbelliferyl-alpha-D-N-acetylneuraminate) substrate. Anal. Biochem. 94, 287-296.
57. Prabakaran, M., Prabhu, N., He, F., Hongliang, Q., Ho, H.T., Qiang, J., Meng, T., Goutama, M., Kwang, J., 2009. Combination therapy using chimeric monoclonal antibodies protects mice from lethal H5N1 infection and prevents formation of escape mutants. PLoS One 4, e5672.
58. Prichard, M.N., Shipman Jr., C., 1990. A three-dimensional model to analyze drug-drug interactions. Antiviral Res. 14, 181-205.
59. Repetto, G., del Peso, A., Zurita, J.L., 2008. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat. Protoc. 3, 1125-1131.
60. Roebroek, A.J., Taylor, N.A., Louagie, E., Pauli, I., Smeijers, L., Snellinx, A., Lauwers, A., Van de Ven, W.J., Hartmann, D., Creemers, J.W., 2004. Limited redundancy of the proprotein convertase furin in mouse liver. J. Biol. Chem. 279, 53442-53450.
61. Sambhara, S., Poland, G.A., 2010. H5N1 Avian influenza: preventive and therapeutic strategies against a pandemic. Annu. Rev. Med. 61, 187-198.
62. Sarac, M.S., Cameron, A., Lindberg, I., 2002. The furin inhibitor hexa-D-arginine blocks the activation of Pseudomonas aeruginosa exotoxin A in vivo. Infect. Immun. 70, 7136-7139.
63. Sarac, M.S., Peinado, J.R., Leppla, S.H., Lindberg, I., 2004. Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo. Infect. Immun. 72, 602-605.
64. Seidah, N.G., Prat, A., 2012. The biology and therapeutic targeting of the proprotein convertases. Nat. Rev. Drug Discov. 11, 367-383.
65. Seo, S., Englund, J.A., Nguyen, J.T., Pukrittayakamee, S., Lindegardh, N., Tarning, J., Tambyah, P.A., Renaud, C., Went, G.T., de Jong, M.D., Boeckh, M.J., 2013. Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics. Antivir. Ther. 18, 377-386.
66. Shiryaev, S.A., Remacle, A.G., Ratnikov, B.I., Nelson, N.A., Savinov, A.Y., Wei, G., Bottini, M., Rega, M.F., Parent, A., Desjardins, R., Fugere, M., Day, R., Sabet, M., Pellecchia, M., Liddington, R.C., Smith, J.W., Mustelin, T., Guiney, D.G., Lebl, M., Strongin, A.Y., 2007. Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens. J. Biol. Chem. 282, 20847-20853.
67. Shortridge, K.F., Zhou, N.N., Guan, Y., Gao, P., Ito, T., Kawaoka, Y., Kodihalli, S., Krauss, S., Markwell, D., Murti, K.G., Norwood, M., Senne, D., Sims, L., Takada, A., Webster, R.G., 1998. Characterization of avian H5N1 influenza viruses from poultry in Hong Kong. Virology 252, 331-342.
68. Sielaff, F., Böttcher-Friebertshäuser, E., Meyer, D., Saupe, S.M., Volk, I.M., Garten, W., Steinmetzer, T., 2011. Development of substrate analogue inhibitors for the human airway trypsin-like protease HAT. Bioorg. Med. Chem. Lett. 21, 4860-4864.
69. Sonnberg, S., Webby, R.J., Webster, R.G., 2013. Natural history of highly pathogenic avian influenza H5N1. Virus Res. 178, 63-77.
70. Steinmetzer, T., Hardes, K., Böttcher-Friebertshäuser, E., Garten, W., 2015. Strategies for the Development of Influenza Drugs: Basis for New Efficient Combination Therapies. Springer, Berlin Heidelberg, pp. 1-39.
71. Stieneke-Gröber, A., Vey, M., Angliker, H., Shaw, E., Thomas, G., Roberts, C., Klenk, H.D., Garten, W., 1992. Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease. EMBO J. 11, 2407-2414.
72. Tarbet, E.B., Maekawa, M., Furuta, Y., Babu, Y.S., Morrey, J.D., Smee, D.F., 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.
73. Tarbet, E.B., Vollmer, A.H., Hurst, B.L., Barnard, D.L., Furuta, Y., Smee, D.F., 2014. In vitro activity of favipiravir and neuraminidase inhibitor combinations against oseltamivir-sensitive and oseltamivir-resistant pandemic influenza A (H1N1) virus. Arch. Virol. 159, 1279-1291.
74. Thomas, G., 2002. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat. Rev. Mol. Cell Biol. 3, 753-766.
75. Walker, J.A., Molloy, S.S., Thomas, G., Sakaguchi, T., Yoshida, T., Chambers, T.M., Kawaoka, Y., 1994. Sequence specificity of furin, a proprotein-processing endoprotease, for the hemagglutinin of a virulent avian influenza virus. J. Virol. 68, 1213-1218.
76. Webster, R.G., Govorkova, E.A., 2014. Continuing challenges in influenza. Ann. N. Y. Acad. Sci. 1323, 115-139.
77. Yen, H.L., Guan, Y., Peiris, M., Webster, R.G., 2008. H5N1 in Asia. In: Klenk, H.D., Matrosovich, M., Stech, J. (Eds.), Avian Influenza. Karger, Basel, pp. 11-26.
78. World Health Organisation, 2015. Cumulative number of confirmed human cases of avian influenza A (H5N1) reported to WHO, Available: http://www.who.int/influenza/human-animal-interface/H5N1-cumulative-table-archives/en/. Downloaded on 06.01.15.