Related Experiment Video
Updated: Jun 14, 2026

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Negative cooperativity drives activity of capsid-directed antivirals against hepatitis B virus
Caleb J Valkner1, Nora Gibes1, Marina Sicheng Xie2
1Molecular and Cellular Biochemistry Department, Indiana University-Bloomington, Bloomington, IN 47405, USA.
Abstract:
Hepatitis B virus capsid protein plays a role in almost every step of viral replication, from self-assembly to genome release. This makes capsid protein an attractive target for antiviral development. Capsid assembly modulators (CAMs) are direct-acting antivirals that bind capsid protein, leading to empty or aberrant complexes instead of an infectious virus. CAMs can also disrupt the capsid, preventing new infection. To understand CAM activity, we examined the energetics of CAM-capsid interaction. We observed negative cooperativity of CAM-binding kinetics and thermodynamics. These correlate with large changes in capsid architecture that presage capsid rupture. We propose that CAMs induce an accumulated strain on the capsid. Understanding the interplay of forces and architecture will help guide the development of CAMs.
Related Concept Videos
Inhibitors Of Virion Release
Antiviral Nucleoside Inhibitors
Inhibitors of Viral Protein Synthesis
Hepatitis
Inhibitors of Virion Maturation and Assembly
Viruses with RNA Genomes

