Trimeris, Inc.

Duke University

Shawn O'Lin Barney

Dennis Michael Lambert

Stephen Robert Petteway

Carl Thomas Wild

Dani Paul Bolognesi

Thomas James Matthews

Alphonse J Langlois

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID NO:1) peptide corresponding to amino acids 638 to 673 of the HIV-1gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Isolated peptides derived from human immunodeficiency virus types 1 and 2 containing fusion inhibitory domains

The present invention relates to peptides which exhibit potent anti-viral activity. In particular, the invention relates to methods of using such peptides as inhibitory of hepatitis B virus ('HepB') transmission to uninfected cells. The peptides used in the methods of the invention are homologs of the DP-178 and DP-107 peptides, peptides corresponding to amino acid residues 638 to 673, and to amino acid residues 558 to 595, respectively, of the HIV-1transmembrane protein (TM) gp41.

Methods for inhibition of membrane-fusion-associated events, including Hepatitis B virus transmission

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID:1) peptide corresponding to amino acids 638 to 673 of the HIV-1gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Fusion proteins comprising DP-178 and other viral fusion inhibitor peptides useful for treating aids

Parainfluenza virus types 1 to 4 (PIV1 to PIV4) are important human pathogens that cause upper and lower respiratory tract infections, particularly in infants and children. The claimed invention is directed toward novel methods for the inhibition of parainfluenza virus transmission to a cell involving the administration of synthetic peptide fusion inhibitors. These inhibitors are derived from the parainfluenza virus and vary in length between 16 to 39 amino acids. The peptides were identified by screening for the presence of fusion inhibitory motifs (e.g., ALLMOTI5, 107x178x4, and PLZIP) within the parainfluenza virus genome. A number of peptides were identified and their fusion inhibitory activities ascertained. These peptides should provide useful antiviral agents.

Methods and compositions for inhibition of membrane fusion-associated events, including HIV transmission

Fusion of the viral envelope, or infected cell membranes with uninfected cell membranes, is an essential step in the viral life cycle. Recent studies involving the human immunodeficiency virus type 1(HIV-1) demonstrated that synthetic peptides (designated DP-107 and DP-178) derived from potential helical regions of the transmembrane (TM) protein, gp41, were potent inhibitors of viral fusion and infection. A computerized antiviral searching technology (C.A.S.T.) that detects related structural motifs (e.g., ALLMOTI 5, 107&times;178&times;4, and PLZIP) in other viral proteins was employed to identify similar regions in the Epstein-Barr virus (EBV). Several conserved heptad repeat domains that are predicted to form coiled-coil structures with antiviral activity were identified in the EBV genome. Synthetic peptides of 16 to 39 amino acids derived from these regions were prepared and their antiviral activities assessed in a suitable in vitro screening assay. These peptides proved to be potent inhibitors of EBV fusion. Based upon their structural and functional equivalence to the known HIV-1 inhibitors DP-107 and DP-178, these peptides should provide a novel approach to the development of targeted therapies for the treatment of EBV infections.

Methods for the inhibition of epstein-barr virus transmission employing anti-viral peptides capable of abrogating viral fusion and transmission

The present invention relates to peptides which exhibit potent anti-viral activity. In particular, the invention relates to methods of using such peptides as inhibitory of respiratory syncytial virus (&ldquo;RSV&rdquo;) transmission to uninfected cells. The peptides used in the methods of the invention are homologs of the DP-178 and DP-107 peptides, peptides corresponding to amino acid residues 638 to 673, and to amino acid residues 558 to 595, respectively, of the HIV-1 transmembrane protein (TM) gp41.

Methods for inhibition of membrane fusion-associated events, including respiratory syncytial virus transmission

Fusion of the viral envelope, or infected cell membranes with uninfected cell membranes, is an essential step in the viral life cycle. Recent studies involving the human immunodeficiency virus type 1 (HIV-1) demonstrated that synthetic peptides (designated DP-107 and DP-178) derived from potential helical regions of the transmembrane (TM) protein, gp41, were potent inhibitors of viral fusion and infection. A computerized antiviral searching technology (C.A.S.T.) that detects related structural motifs (e.g., ALLMOTI5, 107&times;178&times;4, and PLZIP) in other viral proteins was employed to identify similar regions in the respiratory syncytial virus (RSV). Several conserved heptad repeat domains that are predicted to form coiled-coil structures with antiviral activity were identified in the RSV genome. Synthetic peptides of 16 to 39 amino acids derived from these regions were prepared and their antiviral activities assessed in a suitable in vitro screening assay. These peptides proved to be potent inhibitors of RSV fusion. Based upon their structural and functional equivalence to the known HIV-1 inhibitors DP-107 and DP-178, these peptides should provide a novel approach to the development of targeted therapies for the treatment of RSV infections.

Methods for the inhibition of respiratory syncytial virus transmission

The present invention relates to peptides which exhibit antifusogenic and antiviral activities. The peptides of the invention consist of a 16 to 39 amino acid region of a human respiratory syncytial virus protein. These regions were identified through computer algorithms capable of recognizing the ALLMOTI5, 107x178x4, or PLZIP amino acid motifs. These motifs are associated with the antifusogenic and antiviral activities of the claimed peptides.

Human respiratory syncytial virus peptides with antifusogenic and antiviral activities

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID:1) peptide corresponding to amino acids 638 to 673 of the HIV-1.sub.LAI gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Isolated peptides derived from the Epstein-Barr virus containing fusion

Methods for inhibition of membrane fusion-associated events, including

The present invention relates to viral peptides referred to as 'DP107- and DP178-like' peptides. Specifically, the invention relates to isolated influenza A DP107- and DP178-like peptides which are identified by sequence search motif algorithms. The peptides of the invention exhibit antiviral activity believed to result from inhibition of viral induced fusogenic events.

Compositions for inhibition of membrane fusion-associated events,

Screening assays for compounds that inhibit membrane fusion-associated

The present invention relates to peptides which exhibit antifusogenic and antiviral activities. The peptides of the invention consist of a 16 to 39 amino acid region of a simian immunodeficiency virus (SIV) protein. These regions were identified through computer algorithms capable of recognizing the ALLMOTI5, 107.times.178.times.4, or PLZIP amino acid motifs. These motifs are associated with the antifusogenic and antiviral activities of the claimed peptides.

Growing community of inventors

Cary, NC, United States of America

Shawn O'Lin Barney