Duke University

Trimeris, Inc.

National Institutes of Health, a Component of the US Dept. of Health & Human Services

Dani Paul Bolognesi

Thomas James Matthews

Carl Thomas Wild

Michael L Greenberg

Kent J Weinhold

Simon F Lacey

Chin-Ho Chen

Dennis Michael Lambert

Stephen Robert Petteway

Shawn O'Lin Barney

Thomas J Matthews

Georgia D Tomaras

Alphonse J Langlois

Shawn O'lin Barney

Stephen R Petteway

Robert C Gallo

Peter J Fischinger

Annamarie Ranki

Kai Krohn

Gerard W Robey

Flossie Wong-Stall

Cart T Wild

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.

Nucleic acids encoding DP-178 and other viral fusion inhibitor peptides useful for treating aids

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

The present invention relates to a bioactive molecule, herein referred to as the CD8suppressor molecule, that is produced by the CD8subset of human T-lymphocytes and suppresses type-1 human immunodeficiency virus (HIV-1) replication through inhibition of viral transcription. The invention relates to isolation of CD8cell lines and cell clones that produce that antiviral activity and to the development of assay systems for detection of the antiviral activity. The cell lines, cell clones and assay systems, described herein, may be utilized, e.g., to purify, characterize and clone the CD8suppressor molecule. The CD8suppressor molecule may have therapeutic applications for treatment of diseases associated with HIV-1 infection.

Methods for identification of CDS8+ suppressor molecules

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 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.

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

The present invention relates to a bioactive molecule, herein referred to as the CD8 suppressor molecule, that is produced by the CD8 subset of human T-lymphocytes and suppresses type-1 human immunodeficiency virus (HIV-1) replication through inhibition of viral transcription. The invention relates to isolation of clonal CD8 cells lines that produce the antiviral activity and the development of an assay system for detection of the antiviral activity. The clonal cell lines and the assay system, described herein, may be utilized to purify, characterize and clone the CD8 suppressor molecule. The CD8 suppressor molecule may have therapeutic applications for treatment of diseases associated with HIV-1 infection.

Suppressor of HIV-1 replication and transcription

This invention relates to human immunodeficiency virus (HIV) protein fragments which have antiviral activity, and particularly relates to HIV peptides derived from the HIV transmembrane glycoprotein (gp41) which inhibit HIV-induced cell-cell fusion. This invention further relates to methods for the inhibition of enveloped viral infection, and to methods that modulate biochemical processes which involve coiled coil peptide interactions.

Compounds which inhibit HIV replication

The present invention relates to a bioactive molecule, herein referred to as the CD8 suppressor molecule, that is produced by the CD8 subset of human T-lymphocytes and suppresses type-1 human immunodeficiency virus (HIV-1) replication through inhibition of viral transcription. The invention relates to isolation of CD8 cell lines and cell clones that produce that antiviral activity and to the development of assay systems for detection of the antiviral activity. The cell lines, cell clones and assay systems, described herein, may be utilized, e.g., to purify, characterize and clone the CD8 suppressor molecule. The CD8 suppressor molecule may have therapeutic applications for treatment of diseases associated with HIV-1 infection.

Suppressor of HIV replication and transcription

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

Native and recombinant peptides which elicit anti-HIV immune response are provided.

Anti-HIV compositions containing native and recombinant peptides

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP-178 (SEQ ID:1) ptide corresponding to amino acids 638 to 673 of the HIV-1.sub.LAI gp41 protein, and fragments, analogs and homologs of DP-178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Synthetic peptide inhibitors of HIV transmission

The present invention relates to a bioactive molecule, herein referred to as the CD8.sup.+ suppressor molecule, that is produced by the CD8.sup.+ subset of human T-lymphocytes and suppresses type-1 human immunodeficiency virus (HIV-1) replication through inhibition of viral transcription. The invention relates to isolation of clonal CD8.sup.+ cells lines that produce the antiviral activity and the development of an assay system for detection of the antiviral activity. The clonal cell lines and the assay system, described herein, may be utilized to purify, characterize and clone the CD8.sup.+ suppressor molecule. The CD8.sup.+ suppressor molecule may have therapeutic applications for treatment of diseases associated with HIV-1 infection.

Growing community of inventors

Durham, NC, United States of America

Dani Paul Bolognesi