Allosteric conformational changes of human HBV core protein transform its assembly

Area of Science:

• Virology
• Structural Biology
• Drug Discovery

Background:

• Hepatitis B Virus core protein (HBc) is crucial for viral replication, exhibiting polymorphic assembly into icosahedral capsids and aberrant structures.
• The mechanism behind HBc's assembly polymorphism, potentially involving allosteric changes in HBc dimers, remains unclear.

Purpose of the Study:

• To investigate the mechanism of Hepatitis B Virus core protein (HBc) assembly polymorphism.
• To explore the structural basis of HBc assembly using an experimental antiviral drug.

Main Methods:

• Utilized the experimental antiviral drug BAY 41-4109 to induce transformation of HBc assembly.
• Performed structural analyses on HBc dimers from helical tubes, icosahedral capsids, and sheet-like ensembles.

Main Results:

• Successfully transformed HBc assembly from icosahedral capsids to helical tubes using BAY 41-4109.
• Identified distinct differences within the inter-dimer interface of HBc dimers across various assembly forms.
• Disruption of the HBc inter-dimer interface appears to facilitate diverse HBc assembly patterns.

Conclusions:

• The study provides novel structural insights into the assembly mechanism of Hepatitis B Virus.
• Findings offer a strategic foundation for developing new anti-HBV drugs targeting HBc assembly.