Paracelsian, Inc.

Cornell Research Foundation Inc.

Geoffrey D Wheelock

John G Babish

Joseph Rininger

Padmasree Chigurupati

The present invention includes the method of treating a viral infection, specifically one occurring as a result of infection by a human immunodeficiency virus (HIV-1). The method of treatment depends upon the ligand binding of the Ah receptor. Transformation and translocation of the receptor and DNA binding are not required. The study of compounds that interact with the Ah receptor, either as agonists, or antagonists, has resulted in the identification of compounds with useful therapeutic properties through perturbation of viral pathogenic signal transduction pathways. Antagonists of the Ah receptor are more likely candidates for treatment because the toxicity of such compounds is low. Identification of molecules affecting cellular targets, such as the Ah receptor, that inhibit viral pathologic signaling would be of great therapeutic potential as the activity of these molecules is not directed against the virus itself, therefore genetic viral mutation to escape such therapy would be far less likely to occur. The use of secondary compounds for use in combinational, synergistic, therapy is also enclosed. These second compounds are also known to have some effect on the treatment of cellular pathologic changes, together with those compounds found to be effective upon the regulation of the Ah receptor the compounds can more beneficially control virally induced cellular cytopathic changes.

In vitro screening assay for identification of compounds that inhibit

A method of detecting dioxin-like compounds consisting essentially of the group of compounds: polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polychlorinated biphenyls, and structural analogues thereof which exhibit biological activity characteristic of polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polychlorinated biphenyls. The assay includes: 1) an inactive Ah receptor in a form capable of binding to the dioxin-like compounds and being transformed to an active form that forms a complex with ARNT and binds a dioxin responsive element, and 2) a quantity of ARNT sufficient to optimize Ah receptor transformation. A test sample is contacted with the assay under conditions effective to bind the dioxin-like compounds to the Ah receptor and allow transformation of the Ah receptor to an active form that forms a complex with ARNT. The presence of the complex containing the transformed Ah receptor and the ARNT is detected. The presence of the complex containing the transformed Ah receptor and the ARNT is detected with an antibody with a region capable of binding to the ARNT when associated with the complex.

Detection of dioxin-like compounds by detection of transformed Ah

Use of the AH receptor and AH receptor ligands to treat or prevent

The present invention is directed to a method of detecting dioxin-like compounds in a test sample. The test sample is contacted with a heteromer formed from a plurality of proteins, one of which is an inactive Ah receptor. If dioxin-like compounds are present in the test sample, they will bind to the Ah receptor causing it to dissociate from the heteromer as a complex containing active Ah receptor bound to a dioxin-like compound ligand. The presence of the complex is then detected. The process of the present invention can be practiced utilizing solid phase capture, competitive, and sandwich immunoassay test kit formats.

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Ithaca, NY, United States of America

Geoffrey D Wheelock