Artikel
SARS-CoV receptor
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Veröffentlicht: | 26. Mai 2004 |
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Gliederung
Text
Recently we identified angiotensin-converting enzyme 2 (ACE2) as a functional receptor for SARS coronavirus (SARS-CoV) [Ref. 1], and showed that a 193-residue fragment of the SARS-CoV Spike (S) protein is sufficient for its high-affinity association with ACE2 [Ref. 2]. Using murine leukemia virus and lentivirus pseudotyped with the SARS-CoV S protein, we demonstrated the potency of two candidate therapeutics for SARS, one based on soluble ACE2, and the other on the receptor-binding domain of the S protein [Ref. 3].
Rodent orthologs of ACE2 do not support the entry of SARS-CoV efficiently, due to their low affinity for the S protein. NIH3T3 cells expressing human ACE2 allow efficient infection by SARS-CoV. These data indicate that there is no other impediment in murine cells to SARS-CoV infection, and suggest that transgenic mice expressing human ACE2 could serve as a good animal model. Also we have used differences between rodent and human ACE2 to map the S-protein-binding region of human ACE2. Differences in this region of ACE2 among various species provide some insight into the molecular determinants of the adaptation of SARS-CoV to humans.
Among a few open reading frames (ORFs) of SARS-CoV, whose function is unknown, we examined ORF7a, and identified its binding protein. The function of this target protein is under investigation.
References
- 1.
- Wenhui Li, Michael J. Moore, Natalya Vasilieva, Jianhua Sui, Swee Kee Wong, Michael A. Berne, Mohan Somasundaran, John L. Sullivan, Katherine Luzuriaga, Thomas C. Greenough, Hyeryun Choe, Michael Farzan. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. 2003. Nature 426 (27): 450-4
- 2.
- Swee Kee Wong, Wenhui Li, Michael J. Moore, Hyeryun Choe, Michael Farzan. A 193-amino-acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. 2004. J Biol Chem 279(5):3197-201
- 3.
- Michael J. Moore, Tatyana Dorfman, Wenhui Li, Swee Kee Wong, James Coderre, Natalya Vasilieva, Thomas C. Greenough, Michael Farzan, Hyeryun Choe. A lentivirus pseudotyped with the SARS-coronavirus spike protein efficiently infects ACE2-expressing cells. 2004. J Virol