Assay for detection of viral fusion inhibitors
AssigneePanacos Pharmaceuticals, Inc.
InventorsCarl T. Wild, Graham P. Allaway
Life of this patent
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Abstract
The invention is directed to a methods for identifying compounds that inhibit or prevent infection of cells by enveloped viruses such as HIV-1 by preventing or disrupting conformational changes in the viral transmembrane protein that are required for virus fusion with those cells, and the compounds discovered by such methods. The invention also includes using these assays as diagnostic assays to detect antibodies in virus infected individuals that inhibit the viral entry processes.
Claims19
A method for determining the effect of a test compound on the formation of a conformational intermediate of viral entry and/or fusion, comprising contacting a viral envelope protein or glycoprotein with a triggering agent and a candidate compound to form a mixture, and thereafter measuring the effect that the candidate compound has on the formation of said conformational intermediate.
A method for determining the effect of a test compound on the formation of a conformational intermediate of viral entry and/or fusion, comprising
- a. mixing, in an aqueous, buffered solution:
- i. a viral envelope protein or glycoprotein in association with a lipid bilayer, wherein said envelope protein or glycoprotein is necessary and sufficient for viral entry in an intact virus, and wherein said envelope protein or glycoprotein is capable of interacting with one or more receptors on a virus permissive cell;
- ii. one or more virus permissive cells, one or more insoluble or soluble receptors from said virus permissive cells, or a combination thereof;
- and
- iii. a test compound;
- b. measuring the effect of the test compound upon the formation of one or more entry-relevant structures or conformations necessary for virus entry into virus permissive cells.
A method for determining the effect of a test compound on the formation of a conformational intermediate of HIV-1 viral entry and/or fusion, comprising:
- a. mixing, in an aqueous, buffered solution:
- i. HIV-1 envelope glycoproteins gp120/gp41 or fragments thereof in association with a lipid bilayer;
- ii. one or more lymphocytes, or one or more insoluble or soluble receptors from said lymphocytes, or a combination thereof;
- and
- iii. a test compound;
- b. measuring the effect of the test compound upon the formation of one or more entry-relevant structures or conformations necessary for virus entry into virus permissive cells.
Dependencies are inferred from the claim text.