Simulating Hepatitis B Virus antiviral agents

The infectivity of a virus depends on the complete assembly of a protein shell (capsid) around the viral nucleic acid. Molecules which block or alter assembly pathways have the potential to be used as antiviral agents. Recent in vitro experiments have identified a class of small molecules (assembly effectors) that accelerate assembly of Hepatitis B virus (HBV) capsids. In vivo experiments have shown that this acceleration of assembly in vitro correlates to antiviral activity in cells. However, the mechanism by which these molecules alter assembly pathways is unclear. In this talk I will describe a computational model which allows extremely efficient simulation of assembly dynamics of large protein shells. I will then show how application of this model to HBV assembly can elucidate the mechanism of action of assembly effectors. In particular, I will describe how the assembly effectors result in malformed capsid shapes, as seen in experiments.