부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.virusres.2006.03.001 Byline: Bruno Sainz (a), Eric C. Mossel (b), William R. Gallaher (c), William C. Wimley (d), C.J. Peters (b)(e), Russell B. Wilson (f), Robert F. Garry (a) Keywords: Severe acute respiratory syndrome-associated coronavirus; Class I viral fusion protein; Peptide inhibitor; Murine hepatitis virus; Six-helix bundle; Anti-viral Abstract: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the cause of an atypical pneumonia that affected Asia, North America and Europe in 2002-2003. The viral spike (S) glycoprotein is responsible for mediating receptor binding and membrane fusion. Recent studies have proposed that the carboxyl terminal portion (S2 subunit) of the S protein is a class I viral fusion protein. The Wimley and White interfacial hydrophobicity scale was used to identify regions within the CoV S2 subunit that may preferentially associate with lipid membranes with the premise that peptides analogous to these regions may function as inhibitors of viral infectivity. Five regions of high interfacial hydrophobicity spanning the length of the S2 subunit of SARS-CoV and murine hepatitis virus (MHV) were identified. Peptides analogous to regions of the N-terminus or the pre-transmembrane domain of the S2 subunit inhibited SARS-CoV plaque formation by 40-70% at concentrations of 15-30[mu]M. Interestingly, peptides analogous to the SARS-CoV or MHV loop region inhibited viral plaque formation by >80% at similar concentrations. The observed effects were dose-dependent (IC50 values of 2-4[mu]M) and not a result of peptide-mediated cell cytotoxicity. The antiviral activity of the CoV peptides tested provides an attractive basis for the development of new fusion peptide inhibitors corresponding to regions outside the fusion protein heptad repeat regions. Author Affiliation: (a) Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA (b) Department of Microbiology and Immunology,, University of Texas Medical Branch, Galveston, TX 77555, USA (c) Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA (d) Department of Biochemistry, Tulane University Health Sciences Center, New Orleans, LA 70112, USA (e) Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA (f) Autoimmune Technologies, LLC, New Orleans, LA 70112, USA Article History: Received 20 July 2005; Revised 9 February 2006; Accepted 1 March 2006