title: Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion.
abstract: The synthetic peptides DP-107 and DP-178 (T-20), derived from separate domains within the human immunodeficiency virus type 1 (HIV-1) transmembrane (TM) protein, gp4l, are stable and potent inhibitors of HIV-1 infection and fusion. Using a computer searching strategy (computerized antiviral searching technology, C.A.S.T.) based on the predicted secondary structure of DP-107 and DP-178 (T-20), we have identified conserved heptad repeat domains analogous to the DP-107 and DP-178 regions of HIV-1 gp41 within the glycoproteins of other fusogenic viruses. Here we report on antiviral peptides derived from three representative paramyxoviruses, respiratory syncytial virus (RSV), human parainfluenza virus type 3 (HPIV-3), and measles virus (MV). We screened crude preparations of synthetic 35-residue peptides, scanning the DP-178-like domains, in antiviral assays. Peptide preparations demonstrating antiviral activity were purified and tested for their ability to block syncytium formation. Representative DP-178-like peptides from each paramyxovirus blocked homologous virus-mediated syncytium formation and exhibited EC50 values in the range 0.015-0.250 microM. Moreover, these peptides were highly selective for the virus of origin. Identification of biologically active peptides derived from domains within paramyxovirus F1 proteins analogous to the DP-178 domain of HIV-1 gp4l is compelling evidence for equivalent structural and functional features between retroviral and paramyxoviral fusion proteins. These antiviral peptides provide a novel approach to the development of targeted therapies for paramyxovirus infections.
authors.affiliation: Trimeris, Inc., Research Triangle Park, NC 27709, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Lambert
authors.forename: S
authors.initials: S
authors.lastname: Barney
authors.forename: A L
authors.initials: AL
authors.lastname: Lambert
authors.forename: K
authors.initials: K
authors.lastname: Guthrie
authors.forename: R
authors.initials: R
authors.lastname: Medinas
authors.forename: D E
authors.initials: DE
authors.lastname: Davis
authors.forename: T
authors.initials: T
authors.lastname: Bucy
authors.forename: J
authors.initials: J
authors.lastname: Erickson
authors.forename: G
authors.initials: G
authors.lastname: Merutka
authors.forename: S R
authors.initials: SR
authors.lastname: Petteway
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents; D002942:Circular Dichroism; D008459:Measles virus / Q000737:chemistry*; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D010224:Parainfluenza Virus 3, Human / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D012136:Respiratory Syncytial Viruses / Q000737:chemistry*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D014760:Viral Fusion Proteins