Research efforts in my laboratory are concerned with the chemistry and biology of nucleosides, nucleotides, and nucleic acids with particular emphasis on the discovery of novel compounds of antiviral therapeutic interest. Application of molecular recognition concepts to viral genes and enzymes form the basis for our drug design work. Chemoenzymatic methods are utilized for the synthesis of new inhibitors targeted at DNA and RNA viruses including retroviruses such as HIV. Interdisciplinary antiviral studies are performed through national and international collaborative arrangements. One example of success in our quest for new antiviral molecules is the discovery of a compound called an isonucleoside that is potently active against retroviruses. Its triphosphate is one of the most potent known inhibitors of the viral enzyme, HIV reverse transcriptase. A more recent example of success is the discovery of inhibitors of HIV integrase, an enzyme for which very few therapeutically-useful inhibitors are known. This viral enzyme is involved in the incorporation of viral DNA into human chromosomal DNA, the most devastating step in the attack of human cells by HIV. Interdisciplinary research work in my laboratory at UGA has led to the discovery of conceptually new inhibitors of this viral enzyme, which exhibit potent anti-HIV activity. This discovery has been licensed to a Georgia biopharmaceutical company for preclinical and clinical development. Work also continues in my laboratory on antitviral drug discovery targeted against infectious diseases caused by other DNA and RNA viruses.