. The proposed studies will continue efforts to design novel inhibitors of influenza virus replication guided by the structure of the active site of the viral NA as determined from its crystal structure. Benzoic acid derivatives, which are chemically stable and simple to synthesize, have been found to be inhibitory with the most effective compound having an IC-50 of about 10 micromolar. The applicants now plan to further optimize the structure of the benzoic acid derivatives in the hope that they will produce an inhibitor which is active in the nanomolar range. Computer- aided design procedures carried out by the applicants have identified a new pocket in the active site of NA. They plan to utilize this new information and to design a new series of compounds which reach to that site in their effort to further reduce the Ki of their inhibitor. The third approach will be to use what they have learned about the NA binding site to work out the chemistry for the synthesis of alternative compounds.
The third aim i s proposed as a back up in the event that the pharmacological properties of the benzene derivatives prove to be problematic.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01AI031888-05
Application #
2066837
Study Section
Special Emphasis Panel (SRC (86))
Project Start
1995-07-01
Project End
1999-08-31
Budget Start
1995-09-30
Budget End
1996-08-31
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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