Novel Approaches for Targeting Antiviral Agents in the Treatment of Arena-, Bunya-, Flavi-, and Retroviral Infections
Abstract
This contract is devoted to the conjugation of selected antivirals (ribavirin) and immunomodulators (MDP) to neoglycoprotein carriers (poly-L- Lysine or BSA). In vivo virus challenge studies suggest that MDP-BSA and Poly-L- Lysine conjugates are 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. Squirrel monkeys are useful in the evaluation of orally administered immunomodulating agents which have been effective in mice. Studies on a dengue/squirrel monkey model have been initiated and it is anticipated that it should soon be ready for the evaluation of both liposome-encapsulated or conjugated antivirals and immunostimulants. This primate model will be useful in establishing the preclinical efficacy of promising new drugs. A human macrophage antiviral assay is a valuable tool for in vitro evaluation of targeted antivirals and immunostimulants. This assay system has been used to study both RNA and DNA viruses and has allowed us to examine the biological activity of free and conjugated drugs. For example, conjugation of the nucleoside analogue, PMEA, to poly-L-Lysine could be accomplished without any loss of biological activity as determined by the in vitro HSV-1/macrophage assay. Ongoing studies continue to address the in vivo efficacy of conjugated versus liposome-encapsulated antivirals and immunostimulants.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 22, 1989
- Accession Number
- ADA225010
Entities
People
- Abdul Ghaffar
- Eugene P. Mayer
- J. D. Gangemi
Organizations
- University of South Carolina