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(3) Mechanistic Studies of Vaccinia Virus DNA Polymerases and Design/Synthesis of Novel Nucleoside Analog Inhibitors

Concerns about the possible release of smallpox by bioterrorists have led to intensive hunt to find an effective molecule to inhibit viral infection which does not exist yet. Since smallpox virus (variola virus) and the smallpox vaccine (vaccinia virus) are highly homologous, the latter has been used as a very good surrogate model. For example, vaccinia virus DNA polymerase is about 99% identical to its counterpart in smallpox virus. In my laboratory, we are using pre-steady state kinetic methods to investigate the elementary steps of nucleotide incorporation catalyzed by vaccinia virus DNA polymerase. In addition, we are testing more than 140 nucleotide analogs in order to find potent inhibitors which may be effective as anti-smallpox agents.

(1) Pre-Steady State Kinetic Studies of DNA Lesion Bypass Polymerases

(2) Kinetic and Protein-Protein Interaction Studies of Human DNA Polymerases l, µ and TdT

(3) Mechanistic Studies of Vaccinia Virus DNA Polymerases and Design/Synthesis of Novel Nucleoside Analog Inhibitors

(4) Design and Synthesis of Novel Nucleoside Analog Inhibitors

(5) Developing Anti-HCV Peptide-Based Inhibitors

(6) Effects of HCV Protease NS3/4A on Human Kinases Involved in Immune Response