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Updated: Jun 6, 2026
11:34
A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Modeling Reveals How Direct-Acting Antivirals Redirect HBV Capsid Assembly Pathways to Noninfectious Products
Layne B Frechette1, Smriti Pradhan1, Farzaneh Mohajerani1
1Martin Fisher School of Physics, Brandeis University, Waltham, Massachusetts 02453, USA.
Biorxiv : the Preprint Server for Biology
|June 5, 2026
Summary
Capsid assembly modulators (CAMs) show promise for treating Hepatitis B virus (HBV) infections. This study uses a kinetic Monte Carlo model to clarify how CAMs disrupt HBV capsid assembly, paving the way for new antiviral therapies.
Area of Science:
- Virology
- Biophysics
- Computational Biology
Background:
- Hepatitis B virus (HBV) causes chronic liver disease and significant mortality.
- Current HBV treatments lack a definitive cure.
- Capsid assembly modulators (CAMs) are a promising therapeutic class targeting HBV capsid formation.
Purpose of the Study:
- To elucidate the mechanisms by which CAMs influence HBV capsid assembly pathways.
- To utilize a kinetic Monte Carlo (KMC) model to simulate CAM effects on HBV capsid assembly.
- To understand the interplay of kinetics and thermodynamics in directing HBV capsid assembly.
Main Methods:
- Extended a previously developed kinetic Monte Carlo (KMC) model for HBV capsid assembly.
- Simulated the impact of CAMs by modeling their preferential binding to specific subunit interfaces.
- Analyzed simulation trajectories to understand assembly dynamics and product formation.
Main Results:
- The KMC model successfully reproduced experimental HBV capsid assembly product distributions.
- Identified specific CAM binding mechanisms that lead to malformed, non-functional HBV structures.
- Clarified the roles of thermodynamics and kinetics in determining the outcome of HBV capsid assembly.
Conclusions:
- CAMs disrupt HBV capsid assembly by altering subunit interactions and assembly pathways.
- The study provides fundamental insights into viral capsid self-assembly processes.
- Findings support the advancement of CAMs as a potential therapeutic strategy for Hepatitis B virus infections.
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