The spike protein of SARS-CoV - A target for vaccine and therapeutic development

Nature Reviews Microbiology

Volumn 7, Issue 3, 2009, Pages 226-236

  Du, Lanying ^a   He, Yuxian ^a   Zhou, Yusen ^b   Liu, Shuwen ^c   Zheng, Bo Jian ^d   Jiang, Shibo ^a  

^a NEW YORK BLOOD CENTER   (United States)

^b BEIJING INSTITUTE OF MICROBIOLOGY AND EPIDEMIOLOGY   (China)

^c SOUTHERN MEDICAL UNIVERSITY   (China)

^d UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

[No Author keywords available]

Indexed keywords

AMIODARONE; ANGIOTENSIN CONVERTING ENZYME 2; ANTIVIRUS AGENT; BACULOVIRUS VACCINE; CATHEPSIN L INHIBITOR; DNA VACCINE; ENFUVIRTIDE; MONOCLONAL ANTIBODY; NEUTRALIZING ANTIBODY; PARVOVIRUS VACCINE; PARVOVIRUS VECTOR; PEPTIDE; PROTEIN INHIBITOR; PROTEIN P8; PROTEINASE INHIBITOR; RECEPTOR BLOCKING AGENT; RECOMBINANT VACCINE; SEVERE ACUTE RESPIRATORY SYNDROME ANTIBODY; SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS S PROTEIN; SEVERE ACUTE RESPIRATORY SYNDROME VACCINE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; VACCINIA VACCINE; VIRUS ANTIBODY; VIRUS FUSION PROTEIN; VIRUS PROTEIN; VITRONECTIN;

ANTIBODY TITER; ANTIVIRAL ACTIVITY; CONFORMATIONAL TRANSITION; DRUG EFFICACY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INJECTION SITE REACTION; MEMBRANE FUSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN STRUCTURE; PROTEIN TARGETING; RECEPTOR BINDING; REVIEW; SARS CORONAVIRUS; SEVERE ACUTE RESPIRATORY SYNDROME; VIRUS ATTACHMENT; VIRUS ENTRY; VIRUS ENVELOPE; VIRUS REPLICATION; VIRUS STRAIN;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIVIRAL AGENTS; HUMANS; MEMBRANE GLYCOPROTEINS; PEPTIDYL-DIPEPTIDASE A; RNA INTERFERENCE; RNA, SMALL INTERFERING; SARS VIRUS; SEVERE ACUTE RESPIRATORY SYNDROME; VIRAL ENVELOPE PROTEINS; VIRAL VACCINES; VIRUS INTERNALIZATION;

CORONAVIRUS; SARS CORONAVIRUS;

EID: 60749134643     PISSN: 17401526     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrmicro2090     Document Type: Review

References (143)

1. Zhong, N. S. et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. Lancet 362, 1353-1358 (2003).
2. Kuiken, T. et al. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet 362, 263-270 (2003).
3. Marra, M. A. et al. The genome sequence of the SARS-associated coronavirus. Science 300, 1399-1404 (2003).
4. Peiris, J. S. et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361, 1319-1325 (2003).
5. Rota, P. A. et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300 1394-1399 (2003).
6. Guan, Y. et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 302, 276-278 (2003).
7. Li, W. et al. Bats are natural reservoirs of SARS-like coronaviruses. Science 310, 676-679 (2005).
8. Lau, S. K. et al. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc. Natl Acad. Sci. USA 102, 14040-14045 (2005).
9. Skowronski, D. M. et al. Severe acute respiratory syndrome (SARS): a year in review. Annu. Rev. Med. 56, 357-381 (2005).
10. Che, X. Y. et al. A patient with asymptomatic severe acute respiratory syndrome (SARS) and antigenemia from the 2003-2004 community outbreak of SARS in Guangzhou, China. Clin. Infect. Dis. 43, e1-e5 (2006).
11. Fleck, F. SARS virus returns to China as scientists race to find effective vaccine. Bull. World Health Organ. 82, 152-153 (2004).
12. Liang, G. et al. Laboratory diagnosis of four recent sporadic cases of community-acquired SARS, Guangdong Province, China. Emerg. Infect. Dis. 10, 1774-1781 (2004).
13. Shi, Z. & Hu, Z. A review of studies on animal reservoirs of the SARS coronavirus. Virus Res. 133, 74-87 (2008).
14. Liang, W. N. et al. Severe acute respiratory syndrome - retrospect and lessons of 2004 outbreak in China. Biomed. Environ. Sci. 19 445-451 (2006).
15. Normile, D. Infectious diseases. Mounting lab accidents raise SARS fears. Science 304, 659-661 (2004).
16. Orellana, C. Laboratory-acquired SARS raises worries on biosafety. Lancet Infect. Dis. 4, 64 (2004).
17. Mo, H. Y. et al. Evaluation by indirect immunofluorescent assay and enzyme linked immunosorbent assay of the dynamic changes of serum antibody responses against severe acute respiratory syndrome coronavirus. Chin. Med. J. 118, 446-450 (2005).
18. Xu, X. & Gao, X. Immunological responses against SARS-coronavirus infection in humans. Cell. Mol. Immunol. 1, 119-122 (2004).
19. Zhong, X. et al. B-cell responses in patients who have recovered from severe acute respiratory syndrome target a dominant site in the S2 domain of the surface spike glycoprotein. J. Virol. 79, 3401-3408 (2005).
20. Li, T. et al. Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus. PLoS ONE 1, e24 (2006).
21. See, R. H. et al. Severe acute respiratory syndrome vaccine efficacy in ferrets: Whole killed virus and adenovirus-vectored vaccines. J. Gen. Virol. 89, 2136-2146 (2008).
22. Dutta, N. K. et al. Search for potential target site of nucleocapsid gene for the design of an epitope-based SARS DNA vaccine. Immunol. Lett. 118, 65-71 (2008).
23. Jin, H. et al. Induction of Th1 type response by DNA vaccinations with N, M, and E genes against SARS-CoV in mice. Biochem. Biophys. Res. Commun. 328, 979-986 (2005).
24. Zhi, Y. et al. Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein. Virology 335, 34-45 (2005).
25. Buchholz, U. J. et al. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc. Natl Acad. Sci. USA 101, 9804-9809 (2004).
26. Zakhartchouk, A. N. et al. Immunogenicity of a receptor-binding domain of SARS coronavirus spike protein in mice: Implications for a subunit vaccine. Vaccine 25, 136-143 (2007).
27. Zhang, C. Y., Wei, J. F. & He, S. H. Adaptive evolution of the spike gene of SARS coronavirus: Changes in positively selected sites in different epidemic groups. BMC Microbiol. 6, 88 (2006).
28. Weissenhorn, W. et al. Structural basis for membrane fusion by enveloped viruses. Mol. Membr. Biol. 16, 3-9 (1999).
29. Li, F., Li, W., Farzan, M. & Harrison, S. C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 309, 1864-1868 (2005).
30. Wong, S. K., Li, W., Moore, M. J., Choe, H. & Farzan, M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J. Biol. Chem. 279, 3197-3201 (2004).
31. Sainz, B. Jr, Rausch, J. M., Gallaher, W. R., Garry, R. F. & Wimley, W. C. Identification and characterization of the putative fusion peptide of the severe acute respiratory syndrome-associated coronavirus spike protein. J. Virol. 79, 7195-7206 (2005).
32. Sui, J. et al. Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. J. Virol. 79, 5900-5906 (2005).
33. Li, F. et al. Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain. J. Virol. 80, 6794-6800 (2006).
34. Du, L. et al. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity. Biochem. Biophys. Res. Commun. 359, 174-179 (2007).
35. Bosch, B. J., Bartelink, W. & Rottier, P. J. Cathepsin L functionally cleaves the SARS-CoV class I fusion protein upstream of rather than adjacent to the fusion peptide. J. Virol. 82, 8887-8890 (2008).
36. Lai, L. et al. Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase. Curr. Pharm. Des. 12, 4555-4564 (2006).
37. Li, W. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450-454 (2003).
38. Xiao, X., Chakraborti, S., Dimitrov, A. S., Gramatikoff, K. & Dimitrov, D. S. The SARS-CoV S glycoprotein: Expression and functional characterization. Biochem. Biophys. Res. Commun. 312, 1159-1164 (2003).
39. Babcock, G. J., Esshaki, D. J., Thomas, W. D. Jr & Ambrosino, D. M. Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor. J. Virol. 78, 4552-4560 (2004).
40. Prabakaran, P. et al. Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody. J. Biol. Chem. 281, 15829-15836 (2006).
41. Qu, X. X. et al. Identification of two critical amino acid residues of the severe acute respiratory syndrome coronavirus spike protein for its variation in zoonotic tropism transition via a double substitution strategy. J. Biol. Chem. 280, 29588-29595 (2005).
42. Li, W. et al. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 24, 1634-1643 (2005).
43. Sheahan, T., Rockx, B., Donaldson, E., Corti, D. & Baric, R. Pathways of cross-species transmission of synthetically reconstructed zoonotic severe acute respiratory syndrome coronavirus. J. Virol. 82, 8721-8732 (2008).
44. Holmes, K. V. SARS-associated coronavirus. N. Engl. J. Med. 348 1948-1951 (2003).
45. Hofmann, H. et al. S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients. J. Virol. 78, 6134-6142 (2004).
46. Kuhn, J. H., Li, W., Choe, H. & Farzan, M. Angiotensin-converting enzyme 2: A functional receptor for SARS coronavirus. Cell. Mol. Life Sci. 61, 2738-2743 (2004).
47. Prabakaran, P., Xiao, X. & Dimitrov, D. S. A model of the ACE2 structure and function as a SARS-CoV receptor. Biochem. Biophys. Res. Commun. 314, 235-241 (2004).
48. Zhang, Y., Zheng, N., Hao, P., Cao, Y. & Zhong, Y. A molecular docking model of SARS-CoV S1 protein in complex with its receptor, human ACE2. Comput. Biol. Chem. 29, 254-257 (2005).
49. He, Y., Li, J. & Jiang, S. A single amino acid substitution (R441A) in the receptor-binding domain of SARS coronavirus spike protein disrupts the antigenic structure and binding activity. Biochem. Biophys. Res. Commun. 344, 106-113 (2006).
50. Jeffers, S. A. et al. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc. Natl Acad. Sci. USA 101, 15748-15753 (2004).
51. Yang, Z. Y. et al. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J. Virol. 78, 5642-5650 (2004).
52. Han, D. P., Lohani, M. & Cho, M. W. Specific asparagine-linked glycosylation sites are critical for DC-SIGN- and L-SIGN-mediated severe acute respiratory syndrome coronavirus entry. J. Virol. 81, 12029-12039 (2007).
53. Liu, S. et al. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: Implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet 363, 938-947 (2004).
54. Tripet, B. et al. Structural characterization of the SARS-coronavirus spike S fusion protein core. J. Biol. Chem. 279, 20836-20849 (2004).
55. Xu, Y. et al. Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core. J. Biol. Chem. 279, 49414-49419 (2004).
56. Zhou, T. et al. An exposed domain in the severe acute respiratory syndrome coronavirus spike protein induces neutralizing antibodies. J. Virol. 78, 7217-7226 (2004).
57. Keng, C. T. et al. Amino acids 1055 to 1192 in the S2 region of severe acute respiratory syndrome coronavirus S protein induce neutralizing antibodies: Implications for the development of vaccines and antiviral agents. J. Virol. 79, 3289-3296 (2005).
58. Bukreyev, A. et al. Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS. Lancet 363, 2122-2127 (2004).
59. Yang, Z. Y. et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 428, 561-564 (2004).
60. Bisht, H. et al. Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proc. Natl Acad. Sci. USA 101, 6641-6646 (2004).
61. Chen, Z. 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. 79, 2678-2688 (2005).
62. Kam, Y. W. et al. Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcγRII-dependent entry into B cells in vitro. Vaccine 25, 729-740 (2007).
63. He, Y., Li, J., Heck, S., Lustigman, S. & Jiang, S. Antigenic and immunogenic characterization of recombinant baculovirus-expressed severe acute respiratory syndrome coronavirus spike protein: Implication for vaccine design. J. Virol. 80, 5757-5767 (2006).
64. Czub, M., Weingartl, H., Czub, S., He, R. & Cao, J. Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets. Vaccine 23, 2273-2279 (2005).
65. Weingartl, H. et al. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J. Virol. 78, 12672-12676 (2004).
66. Bonavia, A., Zelus, B. D., Wentworth, D. E., Talbot, P. J. & Holmes, K. V. Identification of a receptor-binding domain of the spike glycoprotein of human coronavirus HCoV-229E. J. Virol. 77, 2530-2538 (2003).
67. Kubo, H., Yamada, Y. K. & Taguchi, F. Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein. J. Virol. 68, 5403-5410 (1994).
68. He, Y., Zhou, Y., Siddiqui, P. & Jiang, S. Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry. Biochem. Biophys. Res. Commun. 325, 445-452 (2004).
69. He, Y. et al. Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: Importance for designing SARS vaccines. Virology 334, 74-82 (2005).
70. He, Y. et al. Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: Implication for developing subunit vaccine. Biochem. Biophys. Res. Commun. 324 773-781 (2004).
71. He, Y. et al. Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. J. Immunol. 176, 6085-6092 (2006).
72. Du, L. et al. Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model. Vaccine 25, 2832-2838 (2007).
73. Du, L. et al. Priming with rAAV encoding RBD of SARSCoV S protein and boosting with RBD-specific peptides for T cell epitopes elevated humoral and cellular immune responses against SARS-CoV infection. Vaccine 26, 1644-1651 (2008).
74. Du, L. et al. Recombinant adeno-associated virus expressing the receptor-binding domain of severe acute respiratory syndrome coronavirus S protein elicits neutralizing antibodies: Implication for developing SARS vaccines. Virology 353, 6-16 (2006).
75. Du, L. et al. Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection. J. Immunol. 180, 948-956 (2008).
76. Qin, C. et al. An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus. J. Pathol. 206, 251-259 (2005).
77. He, Y. et al. Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: Revealing the critical antigenic determinants in inactivated SARS-CoV vaccine. Vaccine 24, 5498-5508 (2006).
78. Rockx, B. et al. Synthetic reconstruction of zoonotic and early human severe acute respiratory syndrome coronavirus isolates that produce fatal disease in aged mice. J. Virol. 81, 7410-7423 (2007).
79. Roberts, A. et al. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. PLoS Pathog. 3, e5 (2007).
80. Deming, D. et al. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med. 3, e525 (2006).
81. Vogel, L. N. et al. Utility of the aged BALB/c mouse model to demonstrate prevention and control strategies for severe acute respiratory syndrome coronavirus (SARS-CoV). Vaccine 25, 2173-2179 (2007).
82. Hu, H. et al. Screening and identification of linear B-cell epitopes and entry-blocking peptide of severe acute respiratory syndrome (SARS)-associated coronavirus using synthetic overlapping peptide library. J. Comb. Chem. 7, 648-656 (2005).
83. Han, D. P., Penn-Nicholson, A. & Cho, M. W. Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor. Virology 350, 15-25 (2006).
84. Zheng, B. J. et al. Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus. Antivir. Ther. 10, 393-403 (2005).
85. Jiang, S., Lin, K., Strick, N. & Neurath, A. R. HIV-1 inhibition by a peptide. Nature 365, 113 (1993).
86. Wild, C. T., Shugars, D. C., Greenwell, T. K., Mcdanal, C. B. & Matthews, T. J. Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc. Natl Acad. Sci. USA 91, 9770-9774 (1994).
87. Liu, S., Wu, S. & Jiang, S. HIV entry inhibitors targeting gp41: From polypeptides to small-molecule compounds. Curr. Pharm. Des. 13 143-162 (2007).
88. Chan, D. C. & Kim, P. S. HIV entry and its inhibition. Cell 93 681-684 (1998).
89. Bosch, B. J. et al. Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc. Natl Acad. Sci. USA 101, 8455-8460 (2004).
90. Yuan, K., et al. Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein. Biochem. Biophys. Res. Commun. 319, 746-752 (2004).
91. Mcroy, W. C. & Baric, R. S. Amino acid substitutions in the S2 subunit of mouse hepatitis virus variant V51 encode determinants of host range expansion. J. Virol. 82, 1414-1424 (2008).
92. He, Y., Lu, H., Siddiqui, P., Zhou, Y. & Jiang, S. Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. J. Immunol. 174, 4908-4915 (2005).
93. Lai, S. C. et al. Characterization of neutralizing monoclonal antibodies recognizing a 15-residues epitope on the spike protein HR2 region of severe acute respiratory syndrome coronavirus (SARS-CoV). J. Biomed. Sci. 12, 711-727 (2005).
94. Welt, S. & Ritter, G. Antibodies in the therapy of colon cancer. Semin. Oncol. 26, 683-690 (1999).
95. Nie, Y. et al. Neutralizing antibodies in patients with severe acute respiratory syndrome-associated coronavirus infection. J. Infect. Dis. 190, 1119-1126 (2004).
96. Traggiai, E. et al. An efficient method to make human monoclonal antibodies from memory B cells: Potent neutralization of SARS coronavirus. Nature Med. 10, 871-875 (2004).
97. Zhu, Z. et al. Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. Proc. Natl Acad. Sci. USA 104, 12123-12128 (2007).
98. Coughlin, M. et al. Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse. Virology 361 93-102 (2007).
99. Rockx, B. et al. Structural basis for potent crossneutralizing human monoclonal antibody protection against lethal human and zoonotic severe acute respiratory syndrome coronavirus challenge. J. Virol. 82, 3220-3235 (2008).
100. Sui, J. et al. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc. Natl Acad. Sci. USA 101, 2536-2541 (2004).
101. Van Den Brink, E. N. 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. 79, 1635-1644 (2005).
102. Greenough, T. C. et al. Pneumonitis and multi-organ system disease in common marmosets (Callithrix jacchus) infected with the severe acute respiratory syndrome-associated coronavirus. Am. J. Pathol. 167, 455-463 (2005).
103. Huang, I. C. et al. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J. Biol. Chem. 281, 3198-3203 (2006).
104. Huang, I. C. et al. SARS-CoV, but not HCoV-NL63, utilizes cathepsins to infect cells: Viral entry. Adv. Exp. Med. Biol. 581, 335-338 (2006).
105. Simmons, G. et al. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc. Natl Acad. Sci. USA 102, 11876-11881 (2005).
106. Simmons, G., Rennekamp, A. J. & Bates, P. Proteolysis of SARS-associated coronavirus spike glycoprotein. Adv. Exp. Med. Biol. 581, 235-240 (2006).
107. Stadler, K. et al. Amiodarone alters late endosomes and inhibits SARS coronavirus infection at a postendosomal level. Am. J. Respir. Cell Mol. Biol. 39, 142-149 (2008).
108. Yi, L. et al. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J. Virol. 78 11334-11339 (2004).
109. Kao, R. Y. et al. Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics. Chem. Biol. 11, 1293-1299 (2004).
110. Li, T. et al. siRNA targeting the leader sequence of SARS-CoV inhibits virus replication. Gene Ther. 12, 751-761 (2005).
111. Gitlin, L., Karelsky, S. & Andino, R. Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 418, 430-434 (2002).
112. Wu, C. J., Huang, H. W., Liu, C. Y., Hong, C. F. & Chan, Y. L. Inhibition of SARS-CoV replication by siRNA. Antiviral Res. 65 45-48 (2005).
113. Akerstrom, S., Mirazimi, A. & Tan, Y. J. Inhibition of SARS-CoV replication cycle by small interference RNAs silencing specific SARS proteins, 7a/7b, 3a/3b and S. Antiviral Res. 73, 219-227 (2007).
114. He, M. L. et al. Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus. FEBS Lett. 580, 2414-2420 (2006).
115. Zheng, B. J. et al. Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus. Antivir. Ther. 9 365-374 (2004).
116. Qin, Z. L. et al. Silencing of SARS-CoV spike gene by small interfering RNA in HEK 293T cells. Biochem. Biophys. Res. Commun. 324, 1186-1193 (2004).
117. Zhang, Y. et al. Silencing SARS-CoV spike protein expression in cultured cells by RNA interference. FEBS Lett. 560, 141-146 (2004).
118. Li, B. J. et al. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in rhesus macaque. Nature Med. 11, 944-951 (2005).
119. Simmons, G. et al. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry. Proc. Natl Acad. Sci. USA 101, 4240-4245 (2004).
120. Matsuyama, S., Ujike, M., Morikawa, S., Tashiro, M. & Taguchi, F. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proc. Natl Acad. Sci. USA 102, 12543-12547 (2005).
121. Qinfen, Z. et al. The life cycle of SARS coronavirus in Vero E6 cells. J. Med. Virol. 73, 332-337 (2004).
122. Guo, Y., Korteweg, C., Mcnutt, M. A. & Gu, J. Pathogenetic mechanisms of severe acute respiratory syndrome. Virus Res. 133, 4-12 (2008).
123. Gu, J. & Korteweg, C. Pathology and pathogenesis of severe acute respiratory syndrome. Am. J. Pathol. 170, 1136-1147 (2007).
124. Ding, Y. et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J. Pathol. 203, 622-630 (2004).
125. Frieman, M., Heise, M. & Baric, R. SARS coronavirus and innate immunity. Virus Res. 133, 101-112 (2008).
126. Weiss, S. R. & Navas-Martin, S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol. Mol. Biol. Rev. 69, 635-664 (2005).
127. Holmes, K. V. SARS coronavirus: A new challenge for prevention and therapy. J. Clin. Invest. 111, 1605-1609 (2003).
128. Stertz, S. et al. The intracellular sites of early replication and budding of SARS-coronavirus. Virology 361, 304-315 (2007).
129. Inoue, Y. et al. Clathrin-dependent entry of severe acute respiratory syndrome coronavirus into target cells expressing ACE2 with the cytoplasmic tail deleted. J. Virol. 81, 8722-8729 (2007).
130. Hakansson-Mcreynolds, S., Jiang, S., Rong, L. & Caffrey, M. Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state. J. Biol. Chem. 281, 11965-11971 (2006).
131. Zhao, P. et al. DNA vaccine of SARS-CoV S gene induces antibody response in mice. Acta Biochim. Biophys. Sin. (Shanghai) 36, 37-41 (2004).
132. Wang, S. et al. Identification of two neutralizing regions on the severe acute respiratory syndrome coronavirus spike glycoprotein produced from the mammalian expression system. J. Virol. 79, 1906-1910 (2005).
133. + T cells promote cellular immune responses. Vaccine 25, 6981-6991 (2007).
134. Liu, L. et al. Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus. J. Virol. 81, 4694-4700 (2007).
135. Taylor, D. R. Obstacles and advances in SARS vaccine development. Vaccine 24, 863-871 (2006).
136. Kliger, Y., Levanon, E. Y. & Gerber, D. From genome to antivirals: SARS as a test tube. Drug Discov. Today 10, 345-352 (2005).
137. Wu, X. D. et al. The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells. Cell Res. 14, 400-406 (2004).
138. Ujike, M. et al. Heptad repeat-derived peptides block protease-mediated direct entry from the cell surface of severe acute respiratory syndrome coronavirus but not entry via the endosomal pathway. J. Virol. 82, 588-592 (2008).
139. Yang, Z. Y. et al. Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses. Proc. Natl Acad. Sci. USA 102, 797-801 (2005).
140. Subbarao, K. et al. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice. J. Virol. 78, 3572-3577 (2004).
141. Mitsuki, Y. Y. et al. A single amino acid substitution in the S1 and S2 spike protein domains determines the neutralization escape phenotype of SARS-CoV. Microbes Infect. 10, 908-915 (2008).
142. Ter Meulen, J. et al. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet 363, 2139-2141 (2004).
143. Roberts, A. et al. Therapy with a severe acute respiratory syndrome-associated coronavirusneutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters. J. Infect. Dis. 193, 685-692 (2006).