Ready, set, fuse! the coronavirus spike protein and acquisition of fusion competence

Viruses

Volumn 4, Issue 4, 2012, Pages 557-580

  Heald Sargent, Taylor ^a   Gallagher, Tom ^a  

^a LOYOLA UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Angiotensin converting enzyme 2; Carcinoembryonic antigen; Cathepsin; Coronavirus; Endocytosis; Membrane fusion; Spike protein; Transmembrane protease; Viral pathogenesis; Virus entry

Indexed keywords

ANTIVIRUS AGENT; APROTININ; CAMOSTAT; CATHEPSIN L; ENFUVIRTIDE; GRIFFITHSIN; LECTIN; LEUPEPTIN; MANNAN BINDING LECTIN; PLANT LECTIN; SERINE PROTEINASE; SEVERE ACUTE RESPIRATORY SYNDROME VACCINE; TETRAHYDROQUINOLINE OXOCARBAZATE; TYPE II TRANSMEMBRANE SERINE PROTEINASE; UNCLASSIFIED DRUG; VIRUS RECEPTOR; VIRUS SPIKE PROTEIN;

ACIDIFICATION; ANTIVIRAL ACTIVITY; CELL FUSION; CORONAVIRUS; CORONAVIRUS INFECTION; ENDOCYTOSIS; ENDOSOME; ENZYME ACTIVITY; HUMAN; INFLUENZA; MEMBRANE FUSION; NONHUMAN; PROTEIN DEGRADATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SEVERE ACUTE RESPIRATORY SYNDROME; VACCINATION; VIRUS ENTRY; VIRUS VIRULENCE;

CORONAVIRUS; HUMANS; MEMBRANE GLYCOPROTEINS; SERINE PROTEASES; VIRAL ENVELOPE PROTEINS; VIRUS INTERNALIZATION;

CORONAVIRUS;

EID: 84860245275     PISSN: None     EISSN: 19994915     Source Type: Journal    
DOI: 10.3390/v4040557     Document Type: Review

References (114)

1. Opstelten, D.J.; de Groote, P.; Horzinek, M.C.; Vennema, H.; Rottier, P.J. Disulfide bonds in folding and transport of mouse hepatitis coronavirus glycoproteins. J. Virol. 1993, 67, 7394-7401.
2. Tooze, J.; Tooze, S.; Warren, G. Replication of coronavirus mhv-a59 in saccells: Determination of the first site of budding of progeny virions. Eur. J. Cell Biol. 1984, 33, 281-293.
3. Neuman, B.W.; Adair, B.D.; Yoshioka, C.; Quispe, J.D.; Milligan, R.A.; Yeager, M.; Buchmeier, M.J. Ultrastructure of sars-cov, fipv, and mhv revealed by electron cryomicroscopy. Adv. Exp. Med. Biol. 2006, 581, 181-185.
4. Neuman, B.W.; Adair, B.D.; Yoshioka, C.; Quispe, J.D.; Orca, G.; Kuhn, P.; Milligan, R.A.; Yeager, M.; Buchmeier, M.J. Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy. J. Virol. 2006, 80, 7918-7928.
5. Beniac, D.R.; Andonov, A.; Grudeski, E.; Booth, T.F. Architecture of the sars coronavirus prefusion spike. Nat. Struct. Mol. Biol. 2006, 13, 751-752.
6. Wu, K.; Li, W.; Peng, G.; Li, F. Crystal structure of nl63 respiratory coronavirus receptor-binding domain complexed with its human receptor. Proc. Natl. Acad. Sci. USA 2009, 106, 19970-19974.
7. Li, F.; Li, W.; Farzan, M.; Harrison, S.C. Structure of sars coronavirus spike receptor-binding domain complexed with receptor. Science 2005, 309, 1864-1868.
8. Peng, G.; Sun, D.; Rajashankar, K.R.; Qian, Z.; Holmes, K.V.; Li, F. Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor. Proc. Natl. Acad. Sci. USA 2011, 108, 10696-10701.
9. Wu, K.; Peng, G.; Wilken, M.; Geraghty, R.J.; Li, F. Mechanisms of host receptor adaptation by sars coronavirus. J. Biol. Chem. 2012, 287, 8904-8911.
10. Xu, Y.; Zhu, J.; Liu, Y.; Lou, Z.; Yuan, F.; Liu, Y.; Cole, D.K.; Ni, L.; Su, N.; Qin, L.; et al. Characterization of the heptad repeat regions, hr1 and hr2, and design of a fusion core structure model of the spike protein from severe acute respiratory syndrome (sars) coronavirus. Biochemistry 2004, 43, 14064-14071.
11. Deng, Y.; Liu, J.; Zheng, Q.; Yong, W.; Lu, M. Structures and polymorphic interactions of two heptad-repeat regions of the sars virus s2 protein. Structure 2006, 14, 889-899.
12. Xu, Y.; Liu, Y.; Lou, Z.; Qin, L.; Li, X.; Bai, Z.; Pang, H.; Tien, P.; Gao, G.F.; Rao, Z. Structural basis for coronavirus-mediated membrane fusion. Crystal structure of mouse hepatitis virus spike protein fusion core. J. Biol. Chem. 2004, 279, 30514-30522.
13. Zheng, Q.; Deng, Y.; Liu, J.; van der Hoek, L.; Berkhout, B.; Lu, M. Core structure of s2 from the human coronavirus nl63 spike glycoprotein. Biochemistry 2006, 45, 15205-15215.
14. Wu, K.; Chen, L.; Peng, G.; Zhou, W.; Pennell, C.A.; Mansky, L.M.; Geraghty, R.J.; Li, F. A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses. J. Virol. 2011, 85, 5331-5337.
15. Duquerroy, S.; Vigouroux, A.; Rottier, P.J.; Rey, F.A.; Bosch, B.J. Central ions and lateral asparagine/glutamine zippers stabilize the post-fusion hairpin conformation of the sars coronavirus spike glycoprotein. Virology 2005, 335, 276-285.
16. Lamb, R.A.; Jardetzky, T.S. Structural basis of viral invasion: Lessons from paramyxovirus f. Curr. Opin. Struct. Biol. 2007, 17, 427-436.
17. Luo, Z.; Weiss, S.R. Roles in cell-to-cell fusion of two conserved hydrophobic regions in the murine coronavirus spike protein. Virology 1998, 244, 483-494.
18. Madu, I.G.; Roth, S.L.; Belouzard, S.; Whittaker, G.R. Characterization of a highly conserved domain within the severe acute respiratory syndrome coronavirus spike protein s2 domain with characteristics of a viral fusion peptide. J. Virol. 2009, 83, 7411-7421.
19. Broer, R.; Boson, B.; Spaan, W.; Cosset, F.L.; Corver, J. Important role for the transmembrane domain of severe acute respiratory syndrome coronavirus spike protein during entry. J. Virol. 2006, 80, 1302-1310.
20. Lu, Y.; Neo, T.L.; Liu, D.X.; Tam, J.P. Importance of sars-cov spike protein trp-rich region in viral infectivity. Biochem. Biophys. Res. Commun. 2008, 371, 356-360.
21. Bos, E.C.; Heijnen, L.; Luytjes, W.; Spaan, W.J. Mutational analysis of the murine coronavirus spike protein: Effect on cell-to-cell fusion. Virology 1995, 214, 453-463.
22. Petit, C.M.; Chouljenko, V.N.; Iyer, A.; Colgrove, R.; Farzan, M.; Knipe, D.M.; Kousoulas, K.G. Palmitoylation of the cysteine-rich endodomain of the sars-coronavirus spike glycoprotein is important for spike-mediated cell fusion. Virology 2007, 360, 264-274.
23. Shulla, A.; Gallagher, T. Role of spike protein endodomains in regulating coronavirus entry. J. Biol. Chem. 2009, 284, 32725-32734.
24. Bosch, B.J.; van der Zee, R.; de Haan, C.A.; Rottier, P.J. The coronavirus spike protein is a class i virus fusion protein: Structural and functional characterization of the fusion core complex. J. Virol. 2003, 77, 8801-8811.
25. Tripet, B.; Howard, M.W.; Jobling, M.; Holmes, R.K.; Holmes, K.V.; Hodges, R.S. Structural characterization of the sars-coronavirus spike s fusion protein core. J. Biol. Chem. 2004, 279, 20836-20849.
26. Bosch, B.J.; Martina, B.E.; Van Der Zee, R.; Lepault, J.; Haijema, B.J.; Versluis, C.; Heck, A.J.; De Groot, R.; Osterhaus, A.D.; Rottier, P.J. Severe acute respiratory syndrome coronavirus (sars-cov) infection inhibition using spike protein heptad repeat-derived peptides. Proc. Natil. Acad. Sci. USA 2004, 101, 8455-8460.
27. Liu, I.J.; Kao, C.L.; Hsieh, S.C.; Wey, M.T.; Kan, L.S.; Wang, W.K. Identification of a minimal peptide derived from heptad repeat (hr) 2 of spike protein of sars-cov and combination of hr1-derived peptides as fusion inhibitors. Antiviral Res. 2009, 81, 82-87.
28. Zheng, B.J.; Guan, Y.; Hez, M.L.; Sun, H.; Du, L.; Zheng, Y.; Wong, K.L.; Chen, H.; Chen, Y.; Lu, L.; et al. Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of sars-associated coronavirus. Antiviral Ther. 2005, 10, 393-403.
29. Sturman, L.S.; Ricard, C.S.; Holmes, K.V. Conformational change of the coronavirus peplomer glycoprotein at ph 8.0 and 37 degrees c correlates with virus aggregation and virus-induced cell fusion. J. Virol. 1990, 64, 3042-3050.
30. Gallagher, T.M. A role for naturally occurring variation of the murine coronavirus spike protein in stabilizing association with the cellular receptor. J. Virol. 1997, 71, 3129-3137.
31. Ruch, T.R.; Machamer, C.E. The hydrophobic domain of infectious bronchitis virus e protein alters the host secretory pathway and is important for release of infectious virus. J. Virol. 2011, 85, 675-685.
32. Nieto-Torres, J.L.; Dediego, M.L.; Alvarez, E.; Jimenez-Guardeno, J.M.; Regla-Nava, J.A.; Llorente, M.; Kremer, L.; Shuo, S.; Enjuanes, L. Subcellular location and topology of severe acute respiratory syndrome coronavirus envelope protein. Virology 2011, 415, 69-82.
33. Wilson, L.; McKinlay, C.; Gage, P.; Ewart, G. Sars coronavirus e protein forms cation-selective ion channels. Virology 2004, 330, 322-331.
34. Ortego, J.; Ceriani, J.E.; Patino, C.; Plana, J.; Enjuanes, L. Absence of e protein arrests transmissible gastroenteritis coronavirus maturation in the secretory pathway. Virology 2007, 368, 296-308.
35. Feliciangeli, S.F.; Thomas, L.; Scott, G.K.; Subbian, E.; Hung, C.H.; Molloy, S.S.; Jean, F.; Shinde, U.; Thomas, G. Identification of a ph sensor in the furin propeptide that regulates enzyme activation. J. Biol. Chem. 2006, 281, 16108-16116.
36. de Haan, C.A.; Stadler, K.; Godeke, G.J.; Bosch, B.J.; Rottier, P.J. Cleavage inhibition of the murine coronavirus spike protein by a furin-like enzyme affects cell-cell but not virus-cell fusion. J. Virol. 2004, 78, 6048-6054.
37. Gombold, J.L.; Hingley, S.T.; Weiss, S.R. Fusion-defective mutants of mouse hepatitis virus a59 contain a mutation in the spike protein cleavage signal. J. Virol. 1993, 67, 4504-4512.
38. Yamada, Y.K.; Takimoto, K.; Yabe, M.; Taguchi, F. Acquired fusion activity of a murine coronavirus mhv-2 variant with mutations in the proteolytic cleavage site and the signal sequence of the s protein. Virology 1997, 227, 215-219.
39. Frana, M.F.; Behnke, J.N.; Sturman, L.S.; Holmes, K.V. Proteolytic cleavage of the e2 glycoprotein of murine coronavirus: Host-dependent differences in proteolytic cleavage and cell fusion. J. Virol. 1985, 56, 912-920.
40. Follis, K.E.; York, J.; Nunberg, J.H. Furin cleavage of the sars coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry. Virology 2006, 350, 358-369.
41. de Haan, C.A.; Li, Z.; Lintelo, E.; Bosch, B.J.; Haijema, B.J.; Rottier, P.J. Murine coronavirus with an extended host range uses heparan sulfate as an entry receptor. J. Virol. 2005, 79, 14451-14456.
42. Inoue, Y.; Tanaka, N.; Tanaka, Y.; Inoue, S.; Morita, K.; Zhuang, M.; Hattori, T.; Sugamura, K. Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ace2 with the cytoplasmic tail deleted. J. Virol. 2007, 81, 8722-8729.
43. Thorp, E.B.; Gallagher, T.M. Requirements for ceacams and cholesterol during murine coronavirus cell entry. J. Virol. 2004, 78, 2682-2692.
44. Watanabe, R.; Matsuyama, S.; Taguchi, F. Receptor-independent infection of murine coronavirus: Analysis by spinoculation. J. Virol. 2006, 80, 4901-4908.
45. Miura, H.S.; Nakagaki, K.; Taguchi, F. N-terminal domain of the murine coronavirus receptor ceacam1 is responsible for fusogenic activation and conformational changes of the spike protein. J. Virol. 2004, 78, 216-223.
46. Matsuyama, S.; Taguchi, F. Receptor-induced conformational changes of murine coronavirus spike protein. J. Virol. 2002, 76, 11819-11826.
47. Li, W.; Zhang, C.; Sui, J.; Kuhn, J.H.; Moore, M.J.; Luo, S.; Wong, S.K.; Huang, I.C.; Xu, K.; Vasilieva, N.; et al. Receptor and viral determinants of sars-coronavirus adaptation to human ace2. EMBO J. 2005, 24, 1634-1643.
48. Becker, M.M.; Graham, R.L.; Donaldson, E.F.; Rockx, B.; Sims, A.C.; Sheahan, T.; Pickles, R.J.; Corti, D.; Johnston, R.E.; Baric, R.S.; et al. Synthetic recombinant bat sars-like coronavirus is infectious in cultured cells and in mice. Proc. Natl. Acad. Sci. USA 2008, 105, 19944-19949.
49. Gallagher, T.M.; Parker, S.E.; Buchmeier, M.J. Neutralization-resistant variants of a neurotropic coronavirus are generated by deletions within the amino-terminal half of the spike glycoprotein. J. Virol. 1990, 64, 731-741.
50. Rowe, C.L.; Fleming, J.O.; Nathan, M.J.; Sgro, J.Y.; Palmenberg, A.C.; Baker, S.C. Generation of coronavirus spike deletion variants by high-frequency recombination at regions of predicted rna secondary structure. J. Virol. 1997, 71, 6183-6190.
51. Phillips, J.M.; Weiss, S.R. Pathogenesis of neurotropic murine coronavirus is multifactorial. Trends Pharmacol. Sci. 2011, 32, 2-7.
52. Enjuanes, L.; Sanchez, C.; Gebauer, F.; Mendez, A.; Dopazo, J.; Ballesteros, M.L. Evolution and tropism of transmissible gastroenteritis coronavirus. Adv. Exp. Med. Biol. 1993, 342, 35-42.
53. Schultze, B.; Krempl, C.; Ballesteros, M.L.; Shaw, L.; Schauer, R.; Enjuanes, L.; Herrler, G. Transmissible gastroenteritis coronavirus, but not the related porcine respiratory coronavirus, has a sialic acid (n-glycolylneuraminic acid) binding activity. J. Virol. 1996, 70, 5634-5637.
54. Sanchez, C.M.; Gebauer, F.; Sune, C.; Mendez, A.; Dopazo, J.; Enjuanes, L. Genetic evolution and tropism of transmissible gastroenteritis coronaviruses. Virology 1992, 190, 92-105.
55. Ballesteros, M.L.; Sanchez, C.M.; Enjuanes, L. Two amino acid changes at the n-terminus of transmissible gastroenteritis coronavirus spike protein result in the loss of enteric tropism. Virology 1997, 227, 378-388.
56. Zelus, B.D.; Schickli, J.H.; Blau, D.M.; Weiss, S.R.; Holmes, K.V. Conformational changes in the spike glycoprotein of murine coronavirus are induced at 37 degrees c either by soluble murine ceacam1 receptors or by ph 8. J. Virol. 2003, 77, 830-840.
57. Matsuyama, S.; Taguchi, F. Two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis. J. Virol. 2009, 83, 11133-11141.
58. Grosse, B.; Siddell, S.G. Single amino acid changes in the s2 subunit of the mhv surface glycoprotein confer resistance to neutralization by s1 subunit-specific monoclonal antibody. Virology 1994, 202, 814-824.
59. Ontiveros, E.; Kim, T.S.; Gallagher, T.M.; Perlman, S. Enhanced virulence mediated by the murine coronavirus, mouse hepatitis virus strain jhm, is associated with a glycine at residue 310 of the spike glycoprotein. J. Virol. 2003, 77, 10260-10269.
60. de Haan, C.A.; Lintelo, E.; Li, Z.; Raaben, M.; Wurdinger, T.; Bosch, B.J.; Rottier, P.J. Cooperative involvement of the s1 and s2 subunits of the murine coronavirus spike protein in receptor binding and extended host range. J. Virol. 2006, 80, 10909-10918.
61. Matsuyama, S.; Taguchi, F. Communication between s1n330 and a region in s2 of murine coronavirus spike protein is important for virus entry into cells expressing ceacam1b receptor. Virology 2002, 295, 160-171.
62. Krueger, D.K.; Kelly, S.M.; Lewicki, D.N.; Ruffolo, R.; Gallagher, T.M. Variations in disparate regions of the murine coronavirus spike protein impact the initiation of membrane fusion. J. Virol. 2001, 75, 2792-2802.
63. Sieczkarski, S.B.; Whittaker, G.R. Viral entry. Curr. Top. Microbiol. Immunol. 2005, 285, 1-23.
64. Marsh, M.; Bron, R. Sfv infection in cho cells: Cell-type specific restrictions to productive virus entry at the cell surface. J. Cell Sci. 1997, 110 (Pt 1), 95-103.
65. Gallagher, T.M.; Escarmis, C.; Buchmeier, M.J. Alteration of the ph dependence of coronavirusinduced cell fusion: Effect of mutations in the spike glycoprotein. J. Virol. 1991, 65, 1916-1928.
66. Roos, D.S.; Duchala, C.S.; Stephensen, C.B.; Holmes, K.V.; Choppin, P.W. Control of virus-induced cell fusion by host cell lipid composition. Virology 1990, 175, 345-357.
67. Miyauchi, K.; Kim, Y.; Latinovic, O.; Morozov, V.; Melikyan, G.B. Hiv enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell 2009, 137, 433-444.
68. Sieczkarski, S.B.; Whittaker, G.R. Dissecting virus entry via endocytosis. J. Gen. Virol. 2002, 83, 1535-1545.
69. Nomura, R.; Kiyota, A.; Suzaki, E.; Kataoka, K.; Ohe, Y.; Miyamoto, K.; Senda, T.; Fujimoto, T. Human coronavirus 229e binds to cd13 in rafts and enters the cell through caveolae. J. Virol. 2004, 78, 8701-8708.
70. Choi, K.S.; Aizaki, H.; Lai, M.M. Murine coronavirus requires lipid rafts for virus entry and cellcell fusion but not for virus release. J. Virol. 2005, 79, 9862-9871.
71. Van Hamme, E.; Dewerchin, H.L.; Cornelissen, E.; Verhasselt, B.; Nauwynck, H.J. Clathrinand caveolae-independent entry of feline infectious peritonitis virus in monocytes depends on dynamin. J. Gen. Virol. 2008, 89, 2147-2156.
72. Wang, H.; Yang, P.; Liu, K.; Guo, F.; Zhang, Y.; Zhang, G.; Jiang, C. Sars coronavirus entry into host cells through a novel clathrinand caveolae-independent endocytic pathway. Cell Res. 2008, 18, 290-301.
73. Jaume, M.; Yip, M.S.; Cheung, C.Y.; Leung, H.L.; Li, P.H.; Kien, F.; Dutry, I.; Callendret, B.; Escriou, N.; Altmeyer, R.; et al. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a phand cysteine protease-independent fcgammar pathway. J. Virol. 2011, 85, 10582-10597.
74. Simmons, G.; Reeves, J.D.; Rennekamp, A.J.; Amberg, S.M.; Piefer, A.J.; Bates, P. Characterization of severe acute respiratory syndrome-associated coronavirus (sars-cov) spike glycoprotein-mediated viral entry. Proc. Natil. Acad. Sci. USA 2004, 101, 4240-4245.
75. Qiu, Z.; Hingley, S.T.; Simmons, G.; Yu, C.; Das Sarma, J.; Bates, P.; Weiss, S.R. Endosomal proteolysis by cathepsins is necessary for murine coronavirus mouse hepatitis virus type 2 spike-mediated entry. J. Virol. 2006, 80, 5768-5776.
76. Simmons, G.; Gosalia, D.N.; Rennekamp, A.J.; Reeves, J.D.; Diamond, S.L.; Bates, P. Inhibitors of cathepsin l prevent severe acute respiratory syndrome coronavirus entry. Proc. Natil. Acad. Sci. USA 2005, 102, 11876-11881.
77. Gregory, S.M.; Harada, E.; Liang, B.; Delos, S.E.; White, J.M.; Tamm, L.K. Structure and function of the complete internal fusion loop from ebolavirus glycoprotein 2. Proc. Natil. Acad. Sci. USA 2011, 108, 11211-11216.
78. McReynolds, S.; Jiang, S.; Guo, Y.; Celigoy, J.; Schar, C.; Rong, L.; Caffrey, M. Characterization of the prefusion and transition states of severe acute respiratory syndrome coronavirus s2-hr2. Biochemistry 2008, 47, 6802-6808.
79. Matsuyama, S.; Ujike, M.; Morikawa, S.; Tashiro, M.; Taguchi, F. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proc. Natil. Acad. Sci. USA 2005, 102, 12543-12547.
80. Chandran, K.; Sullivan, N.J.; Felbor, U.; Whelan, S.P.; Cunningham, J.M. Endosomal proteolysis of the ebola virus glycoprotein is necessary for infection. Science 2005, 308, 1643-1645.
81. Bosch, B.J.; Bartelink, W.; Rottier, P.J. Cathepsin l functionally cleaves the severe acute respiratory syndrome coronavirus class i fusion protein upstream of rather than adjacent to the fusion peptide. J. Virol. 2008, 82, 8887-8890.
82. Watanabe, R.; Matsuyama, S.; Shirato, K.; Maejima, M.; Fukushi, S.; Morikawa, S.; Taguchi, F. Entry from the cell surface of severe acute respiratory syndrome coronavirus with cleaved s protein as revealed by pseudotype virus bearing cleaved s protein. J. Virol. 2008, 82, 11985-11991.
83. Yamada, Y.; Liu, D.X. Proteolytic activation of the spike protein at a novel rrrr/s motif is implicated in furin-dependent entry, syncytium formation, and infectivity of coronavirus infectious bronchitis virus in cultured cells. J. Virol. 2009, 83, 8744-8758.
84. Belouzard, S.; Chu, V.C.; Whittaker, G.R. Activation of the sars coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc. Natil. Acad. Sci. USA 2009, 106, 5871-5876.
85. Kam, Y.W.; Okumura, Y.; Kido, H.; Ng, L.F.; Bruzzone, R.; Altmeyer, R. Cleavage of the sars coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro. PLoS One 2009, 4, e7870.
86. Matsuyama, S.; Nagata, N.; Shirato, K.; Kawase, M.; Takeda, M.; Taguchi, F. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease tmprss2. J. Virol. 2010, 84, 12658-12664.
87. Glowacka, I.; Bertram, S.; Muller, M.A.; Allen, P.; Soilleux, E.; Pfefferle, S.; Steffen, I. Tsegaye, T.S.; He, Y.; Gnirss, K.; et al. Evidence that tmprss2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J. Virol. 2011, 85, 4122-4134.
88. Shulla, A.; Heald-Sargent, T.; Subramanya, G.; Zhao, J.; Perlman, S.; Gallagher, T. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J. Virol. 2011, 85, 873-882.
89. Bertram, S.; Glowacka, I.; Muller, M.A.; Lavender, H.; Gnirss, K.; Nehlmeier, I.; Niemeyer, D.; He, Y.; Simmons, G.; Drosten, C.; Soilleux, E.J.; Jahn, O.; Steffen, I.; Pohlmann, S. Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease. J. Virol. 2011, 85, 13363-13372.
90. Szabo, R.; Bugge, T.H. Membrane-anchored serine proteases in vertebrate cell and developmental biology. Annu. Rev. Cell Dev. Biol. 2011, 27, 213-235.
91. Hooper, J.D.; Clements, J.A.; Quigley, J.P.; Antalis, T.M. Type ii transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes. J. Biol. Chem. 2001, 276, 857-860.
92. Paoloni-Giacobino, A.; Chen, H.; Peitsch, M.C.; Rossier, C.; Antonarakis, S.E. Cloning of the tmprss2 gene, which encodes a novel serine protease with transmembrane, ldlra, and srcr domains and maps to 21q22.3. Genomics 1997, 44, 309-320.
93. Kim, T.S.; Heinlein, C.; Hackman, R.C.; Nelson, P.S. Phenotypic analysis of mice lacking the tmprss2-encoded protease. Mol. Cell. Biol. 2006, 26, 965-975.
94. Bottcher, E.; Matrosovich, T.; Beyerle, M.; Klenk, H.D.; Garten, W.; Matrosovich, M. Proteolytic activation of influenza viruses by serine proteases tmprss2 and hat from human airway epithelium. J. Virol. 2006, 80, 9896-9898.
95. Chaipan, C.; Kobasa, D.; Bertram, S.; Glowacka, I.; Steffen, I.; Tsegaye, T.S.; Takeda, M.; Bugge, T.H.; Kim, S.; Park, Y.; Marzi, A.; Pohlmann, S. Proteolytic activation of the 1918 influenza virus hemagglutinin. J. Virol. 2009, 83, 3200-3211.
96. Bottcher-Friebertshauser, E.; Freuer, C.; Sielaff, F.; Schmidt, S.; Eickmann, M.; Uhlendorff, J.; Steinmetzer, T.; Klenk, H.D.; Garten, W. Cleavage of influenza virus hemagglutinin by airway proteases tmprss2 and hat differs in subcellular localization and susceptibility to protease inhibitors. J. Virol. 2010, 84, 5605-5614.
97. Okumura, Y.; Takahashi, E.; Yano, M.; Ohuchi, M.; Daidoji, T.; Nakaya, T.; Bottcher, E.; Garten, W.; Klenk, H.D.; Kido, H. Novel type ii transmembrane serine proteases, mspl and tmprss13, proteolytically activate membrane fusion activity of the hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication. J. Virol. 2010, 84, 5089-5096.
98. Huang, I.C.; Bosch, B.J.; Li, F.; Li, W.; Lee, K.H.; Ghiran, S.; Vasilieva, N.; Dermody, T.S. Harrison, S.C.; Dormitzer, P.R.; et al. Sars coronavirus, but not human coronavirus nl63, utilizes cathepsin l to infect ace2-expressing cells. J. Biol. Chem. 2006, 281, 3198-3203.
99. Du, L.; He, Y.; Zhou, Y.; Liu, S.; Zheng, B.J.; Jiang, S. The spike protein of sars-cov--a target for vaccine and therapeutic development. Nat. Rev. Microbiol. 2009, 7, 226-236.
100. van den Brink, E.N.; Ter Meulen, J.; Cox, F.; Jongeneelen, M.A.; Thijsse, A.; Throsby, M.; Marissen, W.E.; Rood, P.M.; Bakker, A.B.; Gelderblom, H.R.; et al. Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. J. Virol. 2005, 79, 1635-1644.
101. Chen, Z.; Zhang, L.; Qin, C.; Ba, L.; Yi, C.E.; Zhang, F.; Wei, Q.; He, T.; Yu, W.; Yu, J.; et al. Recombinant modified vaccinia virus ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J. Virol. 2005, 79, 2678-2688.
102. Miyoshi-Akiyama, T.; Ishida, I.; Fukushi, M.; Yamaguchi, K.; Matsuoka, Y.; Ishihara, T.; Tsukahara, M.; Hatakeyama, S.; Itoh, N.; Morisawa, A.; et al. Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (sars) coronavirus s protein neutralizes the virus in a rhesus macaque sars model. J. Infect. Dis. 2011, 203, 1574-1581.
103. Mori, T.; O'Keefe, B.R.; Sowder, R.C., 2nd; Bringans, S.; Gardella, R.; Berg, S.; Cochran, P.; Turpin, J.A.; Buckheit, R.W., Jr.; McMahon, J.B.; Boyd, M.R. Isolation and characterization of griffithsin, a novel hiv-inactivating protein, from the red alga griffithsia sp. J. Biol. Chem. 2005, 280, 9345-9353.
104. O'Keefe, B.R.; Giomarelli, B.; Barnard, D.L.; Shenoy, S.R.; Chan, P.K.; McMahon, J.B.; Palmer, K.E.; Barnett, B.W.; Meyerholz, D.K.; Wohlford-Lenane, C.L.; et al. Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein griffithsin against emerging viruses of the family coronaviridae. J. Virol. 2010, 84, 2511-2521.
105. Zhou, Y.; Lu, K.; Pfefferle, S.; Bertram, S.; Glowacka, I.; Drosten, C.; Pohlmann, S.; Simmons, G. A single asparagine-linked glycosylation site of the severe acute respiratory syndrome coronavirus spike glycoprotein facilitates inhibition by mannose-binding lectin through multiple mechanisms. J. Virol. 2010, 84, 8753-8764.
106. van der Meer, F.J.; de Haan, C.A.; Schuurman, N.M.; Haijema, B.J.; Peumans, W.J.; van Damme, E.J.; Delputte, P.L.; Balzarini, J.; Egberink, H.F. Antiviral activity of carbohydratebinding agents against nidovirales in cell culture. Antiviral Res. 2007, 76, 21-29.
107. Shah, P.P.; Wang, T.; Kaletsky, R.L.; Myers, M.C.; Purvis, J.E.; Jing, H.; Huryn, D.M.; Greenbaum, D.C.; Smith, A.B., 3rd; Bates, P.; et al. A small-molecule oxocarbazate inhibitor of human cathepsin l blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293t cells. Mol. Pharmacol. 2010, 78, 319-324.
108. Bahgat, M.M.; Blazejewska, P.; Schughart, K. Inhibition of lung serine proteases in mice: A potentially new approach to control influenza infection. Virol. J. 2011, 8, 27.
109. Lee, M.G.; Kim, K.H.; Park, K.Y.; Kim, J.S. Evaluation of anti-influenza effects of camostat in mice infected with non-adapted human influenza viruses. Arch. Virol. 1996, 141, 1979-1989.
110. Zhirnov, O.P.; Kirzhner, L.S.; Ovcharenko, A.V.; Malyshev, N.A. A clinical effectiveness of aprotinin aerosol in influenza and parainfluenza. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk /Rossiiskaia Akademiia Meditsinskikh Nauk 1996, 26-31.
111. Bottcher-Friebertshauser, E.; Stein, D.A.; Klenk, H.D.; Garten, W. Inhibition of influenza virus infection in human airway cell cultures by an antisense peptide-conjugated morpholino oligomer targeting the hemagglutinin-activating protease tmprss2. J. Virol. 2011, 85, 1554-1562.
112. Zhu, J.; Xiao, G.; Xu, Y.; Yuan, F.; Zheng, C.; Liu, Y.; Yan, H.; Cole, D.K.; Bell, J.I.; Rao, Z.; et al. Following the rule: Formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors. Biochem. Biophys. Res. Commun. 2004, 319, 283-288.
113. Tremblay, C.L.; Kollmann, C.; Giguel, F.; Chou, T.C.; Hirsch, M.S. Strong in vitro synergy between the fusion inhibitor t-20 and the cxcr4 blocker amd-3100. J. Acquir Immune Defic. Syndr. 2000, 25, 99-102.
114. Bosch, B.J.; Rossen, J.W.; Bartelink, W.; Zuurveen, S.J.; de Haan, C.A.; Duquerroy, S.; Boucher, C.A.; Rottier, P.J. Coronavirus escape from heptad repeat 2 (hr2)-derived peptide entry inhibition as a result of mutations in the hr1 domain of the spike fusion protein. J. Virol. 2008, 82, 2580-2585.