The specific objectives of the studies of antiviral selectivity proposed in the contract are: 1. To determine the degree of antiviral selectivity of compounds in human peripheral blood mononuclear cells, in a T cell line (MT2), and in human macrophages. (2) To determine in cell culture if a combined chemotherapeutic approach can be additive or synergistic without increased toxicity. (3) To determine if the selected drugs or combinations are effective in inhibiting AZT-resistant HIV-1. (4) To determine the intracellular levels of the combined drugs (and potential metabolites) in primary human lymphocytes compared to those individual drugs under similar conditions. (5) To determine the biochemical basis for additive or synergistic interactions of the combinations. Additional studies described in the proposal include the following: (1) To determine the intracellular levels of combined drugs (and potential metabolites) in human lymphocytes when drug a is withdrawn at different times after pulsing with radiolabeled compound. (2) To evaluate compounds that are selective against human and non-human retrovirus reverse transcriptases (RTs) to determine if they are specific for HIV-1 RT. (3) To determine the inhibition constant (Ki) and mechanism of inhibition (e.g., competitive, etc.) for the compounds that are selective against the purified enzyme. (4) To determine the type of interaction produced between the new compounds identified as selective anti-HIV-1 RT inhibitors when combined at different ratios with other known anti-HIV-1 compounds. (5) To determine whether the compounds or combination can interfere in the binding of gp120 to CD4.

Project Start
1990-07-09
Project End
1995-07-08
Budget Start
1992-03-23
Budget End
1993-07-08
Support Year
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Emory University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322