Hepatitis B virus is a major pathogen and one of the most prevalent causative agents of cancer in humans. It is estimated that 200-400 million people worldwide suffer from chronic infection by this dsDNA virus. While effective vaccines are available, it remains of significant interest to add to the battery of antiviral therapeutics that can combat the virus.

In collaboration with Prof. Adam Zlotnick (Indiana University), we have begun to apply solution, small-angle X-ray scattering (SAXS) and other biophysical methods including single-molecule fluorescence microscopy to understand the assembly and disassembly of HBV cores and to investigate the mechanism of anti-viral drug-induced core particle disruption. Recent studies of the heteroaryldihydro-pyrimidine (HAP) family of compounds have demonstrated that these drugs bind to the capsid proteins and induce misassembly, thereby arresting the viral life cycle.

The goal of these studies is to understand mechanistically how a complex viral assembly is constructed and how capsid-targeted drug compounds can shunt the assembly reactions off-pathway.