Hepatitis B Virus Polymerase as an Antiviral Drug Target

There are 300 million people in the world who are chronically infected with hepatitis B virus (HBV). Available therapies for the elimination of HBV infection often have a transient effect only. These therapies do not specifically target HBV, and this, in part, is a basis for their limited and variable performances. We will seek to develop targeted antiviral drugs with a particular emphasis on HBV. The product of the HBV pol gene has a central role in viral replication. It has a complex of functions which include reverse transcription, RNase H, DNA priming, and DNA synthesis. Such unique and essential functions make it a prime target for prospective anti-HBV drugs. This program proposes to seek pol gene-associated activities in soluble products from host cells transformed with expression vectors that contain appropriate constructs prepared from the HBV pol gene. These enzymatically active peptides will be used to develop microwell-formatted quantitative assays. Further developments will take these assays into automated high- throughput systems for use in large-scale screening of compounds with prospective inhibitory activity. Such inhibitors, once identified and characterized, will form the bases for the development of targeted anti-HBV drugs.