The present invention provides modified cupredoxin derived peptides with pharmacologic activity that have improved pharmacokinetic properties, and methods to use them to treat mammals suffering from various conditions related to the pharmacologic activities. Modifications of the cupredoxin derived peptides include amino acid sequence variants and structural derivations that increase the plasma half-life of the peptide, increase the specific activity of the pharmacologic activity, decrease immunogenicity, and decrease the biotransformation of the peptides. The modified cupredoxin derived peptides can be used in methods to treat mammals for cancer, conditions related to inappropriate angiogenesis, viral and bacterial infections, and specifically HIV and malaria, conditions related to ephrin signaling, and to deliver cargo compounds, including diagnostic compounds to cancer cell.

The present invention provides a method for identifying whether a compound inhibits entry of a virus into a cell which comprises: (a) obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus; (b) co-transfecting into a first cell (i) the nucleic acid of step (a), and (ii) a viral expression vector which lacks a nucleic acid encoding an envelope protein, and which comprises an indicator nucleic acid which produces a detectable signal, such that the first cell produces viral particles comprising the envelope protein encoded by the nucleic acid obtained from the patient; (c) contacting the viral particles produced in step (b) with a second cell in the presence of the compound, wherein the second cell expresses a cell surface receptor to which the virus binds; (d) measuring the amount of signal produced by the second cell in order to determine the infectivity of the viral particles; and (e) comparing the amount of signal measured in step (d) with the amount of signal produced in the absence of the compound, wherein a reduced amount of signal measured in the presence of the compound indicates that the compound inhibits entry of the virus into the second cell.

HIV-1's ability to enter a transcriptionally dormant state and establish a reservoir of latently infected cells is considered the major barrier to eradicating the virus from infected patients. Stochastic noise (i.e. fluctuations) in an HIV-1 transcriptional positive-feedback loop is one mechanism that enables HIV-1 to establish latency. Here, Applicants demonstrate that small-molecule modulation of noise in HIV-1 gene expression radically perturbs HIV-1 latency.

The present invention relates to an immunogenic composition comprising an antigenic peptide of formula (I) below: Nt-S-X1-X2-X3-K-X4-Ct (I) [SEQ ID No 1], wherein Nt consists of a peptide having from 0 to 50 amino acids in length, Ct consists of a peptide having from 0 to 50 amino acids in length, each of X1 to X4 consists of an amino acid residue, wherein: (i) X1 means the specific amino acid W or (ii) X1 means any amino acid residue excepted W, (i) X2 means the specific amino acid S or (ii) X2 means any amino acid residue excepted S, (i) X3 means the specific amino acid N or (ii) X3 means any amino acid residue excepted N, (i) X4 means the specific amino acid S or (ii) X4 means any amino acid residue excepted S, with the proviso that three out of the four amino acid residues X1, X2, X3 and X4 mean the specific amino acid defined in their respective meaning (i) above, and the remaining amino acid residue among X1 to X4 means any amino acid residue excepted the specific amino acid residue defined in its meaning (i), for preventing and/or treating an infection of an individual with an HIV-1 virus.

Broadly neutralizing antibodies against HIV-1 which specifically bind to gp120 of HIV-1, a method of preparing such antibodies and the use thereof are provided.

A method for determining the risk of cardiovascular disease in a subject having a chronic viral infection includes determining a level of determining a level of at least one lysophophatidic acid (LPA) subtype in the subject, wherein the LPA subtype is selected from the group consisting of LPA 16:0, 18:1, 18:2, and 20:4 and comparing the determined level of the at least one LPA to a control level, wherein an increased level of at least one LPA subtype is indicative of the subject having an increased risk of cardiovascular disease associated with the chronic viral infection.

The present invention relates in general to cellular analysis tools and more particularly to methods for detecting or determining cyclic nucleotide concentrations in samples. Samples containing cyclic nucleotides may be contacted with a cyclic nucleotide-dependent protein kinase and a detection system which includes a substrate for the cyclic nucleotide-dependent protein kinase. The activities in cyclic nucleotide related pathways may be measured using the detection system.

The present invention relates to compositions and methods comprising chemopreventive agents that may be cupredoxin(s) or variants, derivatives and structural equivalents of cupredoxins, and at least one other chemopreventive agent. Specifically, these compositions may comprise azurin from Pseudomonas aeruginosa, and/or the 50-77 residue region of azurin (p28). The compositions of the invention may be used to prevent or inhibit the development of premalignant lesions in mammalian cells, tissues and animals, and thus prevent cancer.

The present application provides specific antibodies that bind to HVEM and that were generated using LAMP technology, which allowed for the presentation of novel, three dimensional epitopes improving the production of anti-HVEM antibodies. In the past, therapeutically effective antibodies directed to HVEM were difficult to generate which the present invention has overcome. Also provided are uses of these antibodies, methods of making these antibodies and polynucleotides and host cells related to these antibodies.

One aspect of the invention provides a system for drug discovery, drug development, drug screening, or drug validation. The system includes: a sample chamber comprising a target protein and a drug candidate that may interfere with the target protein in the sample chamber, wherein the sample chamber is configured to: detect one or more of the following: (a) interference between the drug candidate the target protein and/or (b) one or more dynamics of the drug candidate on the target protein, wherein the one or more dynamics comprise affinity of the drug candidate to the target protein, and select the drug candidate if one or more desirable dynamics is detected. The system includes one or more immobilized surfaces and is configured to detect interactions between the drug candidate and the target protein at the single-molecule level.