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AssigneeEmory University
InventorsRaymond F. Schinazi, Christina Gavegnano
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Compounds, compositions, and methods of treatment and prevention of HIV, including HIV-1 and HIV-2, Dengue, and Chikungunya infection are disclosed. The compounds are TREM-1 inhibitors. Combinations of these TREM-1 inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, JAK inhibitors, macrophage depleting agents, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV, Dengue, or Chikungunya virus in an infected patient.
A method for treating an HIV infection, comprising administering to a patient in need thereof an effective antiviral amount of a TREM-1 inhibitor in combination with HAART.
A method for treating an HIV infection, comprising administering to a patient in need thereof an effective antiviral amount of a TREM-1 inhibitor, wherein the TREM-1 inhibitor is selected from the group consisting of TLT-1, -CDR2 (SAVDRRAPAGRR, SEQ ID NO 1), TLT-1-CDR3 (CMVDGARGPQILHR, SEQ ID NO 2), LR17 (LQEEDAGEYGCMVDGAR, SEQ ID NO 3), LR6-1 (LQEEDA, SEQ ID NO 4), LR6-2 (EDAGEY, SEQ ID NO 5), LR6-3 (GEYGCM, SEQ ID NO 6), LR12 (LQEEDAGEYGCM, SEQ ID NO 7), prodrugs thereof, conjugated versions thereof, deuterated variations thereof, analogs thereof comprising non-naturally occurring amino-acids, functional variations thereof including a different sequence of amino acids but which retain TREM-1 inhibitory activity, analogs thereof in which each amino acid can be, individually, a D or L isomer, and combinations of L-isoforms with D-isoforms thereof, wherein the peptides can optionally be stabilized by micelles.
A method for treating an HIV infection, comprising administering to a patient in need thereof an effective antiviral amount of a TREM-1 inhibitor, wherein the TREM-1 inhibitor is selected from the group consisting of MicroRNA 294, the F-c portion of human IgG (AdTREM-IIg), antibodies directed to the TREM-1 and/or sTREM-1 or TREM-1 and/or sTREM-1 ligands, and fragments thereof which also inhibit TREM-1, small molecules inhibiting the function, activity or expression of TREM-1, siRNAs directed to TREM-1, shRNAs directed to TREM-1, antisense oligonucleotides directed to TREM-1, ribozymes directed to TREM-1, aptamers which bind to and inhibit TREM-1, fusion proteins between human IgGI constant region and the extracellular domain of mouse TREM-1 or that of human TREM-1.
A method of treating or eradicating an HIV infection, comprising:
A method for treating infection by a Dengue virus, comprising administering a TREM-1 inhibitor to a patient in need of treatment or prevention thereof.
A method for treating infection by a Chikungunya virus, comprising administering a TREM-1 inhibitor to a patient in need of treatment or prevention thereof.
A composition for treating HIV, comprising a TREM-1 inhibitor and a second anti-HIV agent, along with a pharmaceutically acceptable carrier or excipient.
Dependencies are inferred from the claim text.