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Journal of Virology, June 2005, p. 7195-7206, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7195-7206.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Identification and Characterization of the Putative Fusion Peptide of the Severe Acute Respiratory Syndrome-Associated Coronavirus Spike Protein

Bruno Sainz Jr.,1 Joshua M. Rausch,2 William R. Gallaher,3 Robert F. Garry,1 and William C. Wimley2*

Department of Microbiology and Immunology, Program in Molecular Pathogenesis and Immunity,1 Department of Biochemistry, Tulane University Health Sciences Center, New Orleans, Louisiana 70112,2 Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 701123

Received 28 October 2004/ Accepted 5 January 2005

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a newly identified member of the family Coronaviridae and poses a serious public health threat. Recent studies indicated that the SARS-CoV viral spike glycoprotein is a class I viral fusion protein. A fusion peptide present at the N-terminal region of class I viral fusion proteins is believed to initiate viral and cell membrane interactions and subsequent fusion. Although the SARS-CoV fusion protein heptad repeats have been well characterized, the fusion peptide has yet to be identified. Based on the conserved features of known viral fusion peptides and using Wimley and White interfacial hydrophobicity plots, we have identified two putative fusion peptides (SARSWW-I and SARSWW-II) at the N terminus of the SARS-CoV S2 subunit. Both peptides are hydrophobic and rich in alanine, glycine, and/or phenylalanine residues and contain a canonical fusion tripeptide along with a central proline residue. Only the SARSWW-I peptide strongly partitioned into the membranes of large unilamellar vesicles (LUV), adopting a ß-sheet structure. Likewise, only SARSWW-I induced the fusion of LUV and caused membrane leakage of vesicle contents at peptide/lipid ratios of 1:50 and 1:100, respectively. The activity of this synthetic peptide appeared to be dependent on its amino acid (aa) sequence, as scrambling the peptide rendered it unable to partition into LUV, assume a defined secondary structure, or induce both fusion and leakage of LUV. Based on the activity of SARSWW-I, we propose that the hydrophobic stretch of 19 aa corresponding to residues 770 to 788 is a fusion peptide of the SARS-CoV S2 subunit.

* Corresponding author. Mailing address: Department of Biochemistry, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL-43, New Orleans, LA 70112. Phone: (504) 988-7076. Fax: (504) 988-2739. E-mail: wwimley{at}tulane.edu.

Journal of Virology, June 2005, p. 7195-7206, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7195-7206.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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