title: A peptide derived from a conserved domain of Sendai virus fusion protein inhibits virus-cell fusion. A plausible mode of action.
abstract: SV-201, a peptide derived from a conserved and potentially amphipathic region (amino acids 201-229) in the Sendai virus ectodomain, specifically inhibited virus-mediated hemolysis only when added to virions prior to their attachment to red blood cells. Sendai virus-mediated hemagglutinin assay in the presence of SV-201 demonstrated that the peptide does not disturb the binding of virions to the target red blood cells. A mutated peptide with 2 amino acids substitution, rendering the peptide neutral, was biologically inactive. A second mutant with 7 amino acids randomized at the N terminus keeping the hydrophobicity of the peptide unaltered was only slightly active. A hydrophobic peptide corresponding to the fusion peptide domain was also inactive. SV-201, the two mutants, and the fusion peptide bind similarly with high affinity to both negatively charged phosphatidylserine/phosphatidylcholine and zwitterionic phosphatidylcholine lipid vesicles, suggesting that the inhibitory effect is not due merely to membrane modulation. Fluorescence studies with rhodamine-labeled peptides and SV-201-induced inhibition assays, demonstrated that the SV-201 binding site is most probably located in the region corresponding to amino acids 201-229 of the Sendai virus fusion protein. The data presented here suggest that SV-201 disturbs a functional domain in the Sendai virus fusion protein, which is most probably associated with the assembly of the fusion protein and/or membrane apposition. The existence of homologous SV-201 regions in other viruses suggests that these regions may have a similar role, and their synthetic counterparts may act as inhibitors for the corresponding viruses.
authors.affiliation: Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: J K
authors.initials: JK
authors.lastname: Ghosh
authors.forename: Y
authors.initials: Y
authors.lastname: Shai
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002459:Cell Fusion / Q000187:drug effects*; D017124:Conserved Sequence; D004912:Erythrocytes / Q000821:virology; D006387:Hemagglutination, Viral / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D017433:Protein Structure, Secondary; D018108:Respirovirus; D013050:Spectrometry, Fluorescence; D013054:Spectrophotometry, Atomic; D014760:Viral Fusion Proteins / Q000737:chemistry*; D014764:Viral Proteins / Q000138:chemical synthesis* / Q000235:genetics / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; C111491:SV 201 protein, Sendai virus; D014760:Viral Fusion Proteins; D014764:Viral Proteins