Provided are compositions and methods for identifying test agents as candidate for use in reducing hepatitis B virus (HBV). The methods involve a) introducing at least one test agent into mammalian cells, the cells having one or more plasmids that encode an HBV genome, wherein the genome includes a segment encoding a mutated HBV core (HBc), wherein the HBc mutation is L60A, I126A, K96A or a combination thereof. The test agent is allowed to be in contact with the mammalian cells for a period of time. Subsequently, amounts of HBV cccDNA in the mammalian cells are determined. The method can be performed in vitro or in vivo. A reduction in cccDNA relative to a control indicates the test agent in the test container is a candidate for reducing HBV in an individual. Cell cultures divided into reaction containers that each contain a distinct test agent are also included.
