DRUG DISCOVERY GROUP FOR THE TREATMENT OF AIDS

The United States Army Medical Research Institute of Infectious
Diseases - National Cooperative Drug Discovery Group
(USAMRIID-NCDDG) consists of several collaborating components
to expeditiously test, evaluate and recommend agents, or
combination of agents, of therapeutic value for the treatment of
human ARC-AIDS. Each component selected for its expertise
performs specific tasks. The USAMRIID-NCDDG consists of a (1)
network of academic, industrial, government and chemical
synthesis contract laboratories which will supply over 1,500
compound per year for testing; (2) several inhouse and extramural
laboratories are engaged in screening drugs and biologicals in
vitro and in vivo for efficacy and immunomodulator activity; (3)
the Technassociates contract provides a comprehensive data base
management system for storing, searching, and retrieving
molecular and reaction data, increasing the efficiency and
productivity of all members of the USAMRIID-NCDDG. Test data
from the testing laboratories are entered into the data base
through which; redundant testing of similar compounds are
eliminated; structure activity relationship models can be
generated allowing for molecular modeling and further judicial
selection of candidate drugs for screening or for synthesis; (4)
through crystallography and molecular modeling the structural
elucidation of isolated HIV proteins (regulatory and coat proteins),
enzymes, gene products and, monoclonal antibodies to these
isolates, will provide information for the rational design for
developing prophylactic and therapeutic drugs specific treatment
of AIDS; (5) two murine retrovirus models will be employed for
the evaluation of compounds selected from the screening
programs or, of unknown antiviral or immunoregulatory activity.
In vivo rather than in vitro models are best suited to assess drugs
or biologicals for immunoregulatory capacity since many agents
regulate cellular immunity through stimulation of cytokines in
vivo; (6) a collaborative program within USAMRIID will be
devoted to establishing a simian HTLV model using the
characterized simian HIV III virus leading to an optimally
consistent model for the human disease. Other viruses models
will be developed as appropriate strains of viruses are isolated and
characterized. The ultimate aim is to establish a reproducible
simian AIDS model for evaluating immunomodulators and antiviral
agents. This multifaceted program reflects the total commitment
of the USAMRIID-NCDDG to perform all phases from drug
development testing, evaluating and to perform clinical studies.