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.
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