Negative cooperativity drives activity of capsid-directed antivirals against hepatitis B virus

Science Advances 2026 Open access

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Authors: Caleb J. Valkner, Nora Gibes, Marina Sicheng Xie, Smita Nair, Shiv Kumar, Samson Francis, Balasubramanian Venkatakrishnan, Irina B. Tsvetkova, Angela Patterson, VanNieuwenhze Michael, Bogdan Dragnea, Joseph Che‐Yen Wang
+1 more Adam Zlotnick
DOI: 10.1126/sciadv.aed6483
Cited by: 1
References: 75

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.

Fields of Study & Subjects

Bacteriophages and microbial interactions Microtubule and mitosis dynamics Hepatitis B Virus Studies

Publication details

Journal / source
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Volume
12
Issue
24
Pages
eaed6483–eaed6483
Publication date
12 June 2026
Language
EN