Chronic hepatitis B virus (HBV) infection is presently incurable, affects 250 million people and is a major cause of liver failure.

Our HBV research is focused on simulations of small oligomers of HBV capsid protein (Cp). Previous research have shown that capsid assembly modulators (CAMs) can be effective drugs against HBV at sub-nanomolar concentrations. They induce conformation changes in the small Cp complexes, preventing normal capsid assembly. Unfortunately, the most potent in vitro scaffold, heteroaryldihydropyrimidine (HAP), and its derivatives are also toxic.

We use MD simulations to study the underlying allosteric conformational changes of Cp complexes that lead to capsid formation and to understand why HAP scaffolds are so efficient at preventing normal assembly. We are using the results from our simulations to design new CAMs with lower toxicity de novo.

The experimental part of the work is made possible through to collaboration with Dr. Ray Schinazi at Emory University.