Targeting the Achilles heel of the hepatitis B virus: a review of current treatments against covalently closed circular DNA

Chronic infection with hepatitis B virus (HBV) often leads to the development of liver cancer and cirrhosis, creating immense sociological, clinical and economic burdens worldwide. Although current anti-HBV medications manage to control the disease progression and help restore normal liver functions, they often fail to eliminate the virus completely. A major reason for this failure is the presence of a stable viral genome in the hepatocyte nucleus: the covalently closed circular DNA (cccDNA). Targeting HBV cccDNA is a promising approach that could lead to a complete cure. Here, we review various research approaches that are directed toward eliminating HBV cccDNA. This is a brief, yet comprehensive, summary of current state-of-the-art developments in this emerging area of interest.