Novel Approaches for Targeting Antiviral Agents in the Treatment of Arena-, Bunya-, Flavi-, and Retroviral Infections.

摘要

SUMMARY YEAR 1 - The first year of this contract was devoted to the conjugation of selected antivirals (ribavirin and PMEA) immunomodulators (MDP) to neoglycoprotein carriers (poly-L-lysine or BSA). our in vivo virus challenge studies suggest that MDP-BSA and Poly-L-lysine conjugates were more effective than free MDP in enhancing resistance to HSV-1 hepatitis and pneumonitis. Moreover, conjugated MDP was more effective in enhancing RES function than was free drug. In addition, conjugated PMEA was more effective than free drug in reducing virus titers in lungs of infected Squirrel monkeys. Monkeys were shown to be useful in the evaluation of an orally administered immunomodulating agent, CL 246738, as evidenced by the induction of serum interferon. Thus, this primate model was selected for the preclinical evaluation of promising new drugs (see below). Viruses, Neoglycoproteins, BD, RAI, Liposomes, Antiviral, Immunostimulated, Lab Animals.