Abstract: This invention provides a modified gp140 envelope polypeptide of an HIV-1 isolate comprising a gp120 polypeptide portion comprising consecutive amino acids and a gp41 ectodomain polypeptide portion comprising consecutive amino acids, said gp41 ectodomain polypeptide portion being modified to comprise isoleucine (I) at an amino acid position equivalent to amino acid position 535; glutamine (Q) at an amino acid position equivalent to amino acid position 543; serine (S) at an amino acid position equivalent to amino acid position 553; lysine (K) at an amino acid position equivalent to amino acid position 567; and arginine (R) at an amino acid position equivalent to amino acid position 588, the amino acid positions being numbered by reference to the HIV-1 isolate KNH1144. This invention also provides nucleic acids encoding such a polypeptide, vectors, host cells, trimeric complexes and compositions thereof.

Abstract: This invention relates to synthesis of (R),(R)-2,2?-bis-MNTX, as shown in Formula (I), and related methods and products.

Abstract: This invention provides methods for inhibiting fusion of HIV-1 to CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited. This invention also provides methods for inhibiting HIV-1 infection of CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited, thereby inhibiting the HIV-1 infection. This invention provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells. This invention also provides pharmaceutical compositions comprising an amount of the non-chemokine agent capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells effective to prevent fusion of HIV-1 to CD4+ cells and a pharmaceutically acceptable carrier.

Abstract: This invention provides: agents determined to be capable of specifically inhibiting the fusion of a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell, but not a T cell-tropic isolate of HIV-1 to a CD4+ cell; and agents determined to be capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 to a CD4+ cell, but not a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell. This invention also provides: agents capable of specifically inhibiting the fusion of a macrophage tropic primary isolate of HIV-1 with a CD+ cell susceptible to infection by a macrophage-tropic primary isolate of HIV-1; and agents capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 with a CD4+ cell susceptible to infection by a T cell-tropic isolate of HIV-1. The agents include but are not limited to antibodies.

Abstract: This invention provides agents determined to be capable of inhibiting the fusion of a macrophage-tropic primary isolate of HIV-1 to a CD4+cell and agents determined to be capable of inhibiting the fusion of a T cell-tropic isolate of HIV-1 to a CD4+cell. This invention also provides methods to identify such agents. This invention further provides methods of inhibiting fusion of a macrophage-tropic primary isolate of HIV-1 with a CD+ cell and methods of inhibiting fusion of a T cell-tropic isolate of HIV-1 with a CD4+cell susceptible to infection by a T cell-tropic isolate of HIV-1.

Abstract: This invention provides methods for inhibiting fusion of HIV-1 to CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited. This invention also provides methods for inhibiting HIV-1 infection of CD4+ cells which comprise contacting CD4+ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4+ cells is inhibited, thereby inhibiting the HIV-1 infection. This invention provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells. This invention also provides pharmaceutical compositions comprising an amount of the non-chemokine agent capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4+ cells effective to prevent fusion of HIV-1 to CD4+ cells and a pharmaceutically acceptable carrier.

Abstract: The invention is directed an anti-CCR5 antibody which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising an expression product of either a plasmid designated pVg1:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmid designated pVg1:HuPRO140 (mutB+D+I)-VH (ATCC Deposit Designation PTA-4099) or a fragment thereof which binds to CCR5 on the surface of a human cell.

Abstract: This invention provides a composition which comprises an admixture of three compounds, wherein: (a) one compound is an antibody which binds to a CCR5 receptor; (b) one compound retards attachment of HIV-1 to a CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell; and (c) one compound retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate; wherein the relative mass ratio of any two of the compounds in the admixture ranges from about 100:1 to about 1:100, the composition being effective to inhibit HIV-1 infection of the CD4+ cell. This invention also provides a method of inhibiting HIV-1 infection of a CD4+ cell which comprises contacting the CD4+ cell with an amount of the composition of the subject invention effective to inhibit HIV-1 infection of the CD4+ cell so as to thereby inhibit HIV-1 infection of the CD4+ cell.

Abstract: This invention relates to stereoselective synthesis of R-MNTX and intermediates thereof, pharmaceutical preparations comprising R-MNTX or intermediates thereof and methods for their use.

Abstract: The invention is directed an anti-CCR5 antibody which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO14O-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising an expression product of either a plasmid designated pVgl:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmic designated pVgl:HuPRO140 (mutB+D+I)-VH (ATCC Deposit Designation PTA-4099) or a fragment thereof which binds to CCR5 on the surface of a human cell.

Abstract: This invention provides an isolated nucleic acid which comprises a nucleotide segment having a sequence encoding a viral envelope protein comprising a viral surface protein and a corresponding viral transmembrane protein wherein the viral envelope protein contains one or more mutations in amino acid sequence that enhance the stability of the complex formed between the viral surface protein and transmembrane protein. This invention also provides a viral envelope protein comprising a viral surface protein and a corresponding viral transmembrane protein wherein the viral envelope protein contains one or more mutations in amino acid sequence that enhance the stability of the complex formed between the viral surface protein and transmembrane protein. This invention further provides methods of treating HIV-1 infection.

Abstract: This invention relates to S-MNTX, methods of producing S-MNTX, pharmaceutical preparations comprising S-MNTX and methods for their use.

Abstract: Novel (R)—N-stereoisomers of 7,8-saturated-4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the (R)—N-stereoisomers of 7,8-saturated-4,5-epoxy-morphinanium analogs and methods for their pharmaceutical uses are also disclosed. Such analogs are disclosed as being useful in treating, among varying conditions, opioid-induced constipation.

Abstract: This invention provides a DNA which upon transcription produces an RNA encoding a modified HIV-1 gp140 polypeptide, which polypeptide upon cleavage produces a modified gp120 and a modified ectodomain of gp41 which together form a complex exhibiting enhanced binding to HIV-1 neutralizing antibodies and reduced binding to HIV-1 non-neutralizing antibodies, wherein the modifications comprise an A492C mutation in gp120 and a T596C mutation in gp41, said mutations being numbered by reference to the HIV-1 isolate JR-FL, and resulting in a disulfide bond between gp120 and ectodomain gp41 which stabilizes the otherwise non-covalent gp120-gp41 interaction.

Abstract: This invention provides a method of inhibiting HCV infection of a cell susceptible to HCV infection which comprises contacting the cell with an amount of a compound effective to inhibit binding of an HCV envelope glycoprotein to a DC-SIGN protein present on the surface of the cell, so as to thereby inhibit HCV infection of the cell susceptible to HCV infection. This invention provides a method of inhibiting HCV infection of a cell susceptible to HCV infection which comprises contacting the cell with an amount of a compound effective to inhibit binding of an HCV envelope glycoprotein to a DC-SIGNR protein present on the surface of the cell, so as to thereby inhibit HCV infection of the cell susceptible to HCV infection. Compounds of the present invention inhibit HCV infection of cells susceptible to HCV infection.

Abstract: Novel N-oxides of 4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

Abstract: Novel (S)-N-stereoisomers of 7,8-saturated-4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the (S)-N-stereoisomers of 7,8-saturated-4,5-epoxy-morphinanium analogs and methods for their pharmaceutical uses are also disclosed. Such analogs are disclosed as being useful in treating, among varying conditions, hypermotility of the gastrointestinal tract.

Abstract: Novel 7,8-saturated-4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the 7,8-saturated-4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

Abstract: The present invention concerns a modified nucleic acid molecule comprising a nucleotide sequence coding for a full length hepatitis C virus (HCV) glycoprotein selected from the group consisting of E1 glycoprotein and E1/E2 glycoprotein heterodimer, this molecule having at least one nucleotide alteration, wherein, due to this alteration, at least one RNA splice site selected from the group consisting of RNA splice acceptor and RNA splice donor sites is eliminated from the coding sequence. The invention is also directed to methods for expressing on the surface of a cell and a pseudovirion an HCV glycoprotein, wherein the majority of the glycoprotein is full length. The invention further provides a cell and a pseudovirion expressing such glycoprotein. The invention still further provides a method for determining whether an agent inhibits HCV fusion with and entry into a target cell. The invention also provides an agent that inhibits HCV fusion with and entry into a target cell.

Abstract: This invention provides an antibody capable of specifically inhibiting the fusion of an HIV-1 envelope glycoprotein+ cell with an appropriate CD4+ cell without cross reacting with the HIV-1 envelope glycoprotein or CD4 and capable of inhibiting infection by one or more strains of HIV-1. This antibody is then used to identify a molecule which is important for HIV infection. Different uses of the antibody and the molecule are described.