Identification of anti-protozoal agents
AssigneePresident and Fellows of Harvard College for Inventors Westwood and Mitchison
InventorsNicholas J. Westwood, Gary E. Ward, Kimberly L. Carey, Timothy J. Mitchinson
Life of this patent
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Abstract
The present invention provides novel assay systems and methods for monitoring cell invasion by protozoal parasites. The present invention further provides methods of using these assays systems to identify compounds that treat or prevent protozoal infection. The present invention further provides pharmaceutical compositions that have anit-protozoal activity and methods of treating infections.
Claims154
An assay system for detecting invasion of a cell by a protozoa, comprising:
- a cell and a protozoa capable of infecting the cell;
- a first antibody that is capable of binding to the protozoa;
- and
- a second antibody that is capable of binding to the protozoa.
A method of detecting invasion of a cell by a protozoa, comprising steps of:
- contacting cells with a protozoal parasite for a time sufficient to allow invasion of the cells by the parasite;
- contacting protozoal parasites that are external to the cells with a first antibody that is capable of binding to the protozoa
- permeabilizing the cells;
- contacting protozoal parasites that are external and internal to the cells with a second antibody that is capable of binding to the protozoal parasites;
- and
- detecting the first and second antibodies.
An assay system for detecting invasion of a cell by a protozoa, comprising:
- a cell and a labeled protozoa capable of infecting the cell;
- and
- a means of detecting protozoa that do not infect the cell.
A method of detecting invasion of a cell by a protozoa, comprising steps of:
- contacting cells with a labeled protozoal parasite for a time sufficient to allow invasion of the cells by the parasite;
- contacting protozoal parasites that are external to the cell with an antibody that is capable of binding to the protozoa;
- and
- detecting the number of protozoal parasites that are internal to the cell.
A method of identifying an inhibitor of protozoal infection, comprising steps of:
- contacting cells with a compound and a protozoal parasite for a time sufficient to allow invasion of the cells by the parasite;
- detecting the protozoal parasites that are external to the cell, an increase in the number of external parasites in the presence of compound compared to the absence of compound indicating the identification of an inhibitor of protozoal infection.
A method of identifying an activator of protozoal infection, comprising steps of:
- contacting cells with a compound and a protozoal parasite for a time sufficient to allow invasion of the cells by the parasite;
- detecting the protozoal parasites that are internal to the cell, an increase in the number of internal parasites in the presence of compound compared to the absence of compound indicating the identification of an activator of protozoal infection.
A method of treating a protozoal infection, comprising:
- providing a pharmaceutical composition containing a protozoal inhibitor;
- and
- administering the composition to a patient in need thereof.
A pharmaceutical composition comprising a pharmaceutical agent selected from the group consisting of:
- the molecules provided in FIG. 6 (panels A-N) in an amount sufficient to inhibit protazoal parasitic infection and a pharmaceutically acceptable carrier, wherein the carrier is not dimethylsulfoxide (DMSO).
A method for treating an Apicomplexan parasitic infection, comprising:
- administering to a subject in need of such treatment, an effective amount of an Apicomplexan parasite inhibitor to treat the Apicomplexan parasitic infection.
A method for preventing an Apicomplexan parasitic infection, comprising:
- administering to a subject in need of such treatment, an effective amount of an Apicomplexan parasite inhibitor to prevent Apicomplexan parasitic infection.
A method for treating an Apicomplexan parasitic infection, comprising:
- administering to a cell in need of such treatment, an effective amount of an Apicomplexan parasite inhibitor to treat the Apicomplexan parasitic infection in the cell.
A method for preventing an Apicomplexan parasitic infection, comprising:
- administering to a cell in need of such treatment, an effective amount of an Apicomplexan parasite inhibitor to prevent Apicomplexan parasitic infection in the cell.
A method for augmenting an Apicomplexan parasitic infection, comprising:
- administering to a cell exposed to an Apicomplexan parasite an effective amount of an enhancer of Apicomplexan parasite invasion to augment an Apicomplexan parasitic infection.
A method of processing a material contaminated with Apicomplexan parasitic protozoa comprising,
- contacting the material with an Apicomplexan parasite inhibitor to reduce the level of Apicomplexan parasite contamination of the material.
A method of processing a material to prevent contamination with Apicomplexan parasitic protozoa comprising,
- contacting the material with an Apicomplexan parasite inhibitor to prevent contamination with Apicomplexan parasitic protozoa.
A pharmaceutical composition comprising an effective amount of a pharmaceutical agent selected from the group consisting of:
- the molecules provided in FIG. 6 (panels A-N) capable of inhibiting an Apicomplexan protozoa, and a pharmaceutically acceptable carrier, wherein the carrier is not dimethylsulfoxide (DMSO).
A pharmaceutical composition comprising an effective amount of a pharmaceutical agent selected from the group consisting of:
- the molecules provided in FIG. 6 (panels A-N) capable of inhibiting Toxoplasma gondii, and a pharmaceutically acceptable carrier, wherein the carrier is not dimethylsulfoxide (DMSO).
Dependencies are inferred from the claim text.