This proposal is for the development of effective, nontoxic drugs for the treatment of influenza and herpes virus infections. Nonionic oligonucleotide analogs will be prepared by chemistry under development, or already developed, in these laboratories. The base sequences of these analogs are complementary to (""""""""antisense"""""""") mRNAs that code for proteins vital for viral replication. Nonionic inhibitors of the influenza viral polymerase will also be prepared. These sequences are based on our current understanding of the molecular biology of the influenza and herpes viruses. Potential inhibitors will be evaluated in the appropriate in vitro systems, primarily virus infected cells in culture, and compounds with sufficient activity will be tested against infections in experimental animal models and in embryonated eggs. Compounds with in vivo activity will then be developed for clinical trial (preclinical pharmacology and toxicology studies).
