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| Title | Negative cooperativity drives activity of capsid-directed antivirals against hepatitis B virus. |
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| Journal, issue, pages | Sci Adv, Vol. 12, Issue 24, Page eaed6483, Year 2026 |
| Publish date | Jun 12, 2026 |
Authors | Caleb J Valkner / Nora Gibes / Marina Sicheng Xie / Smita Nair / Shiv Kumar / Samson Francis / Balasubramanian Venkatakrishnan / Irina Tsvetkova / Angela Patterson / Michael VanNieuwenhze / Bogdan Dragnea / Joseph Che-Yen Wang / Adam Zlotnick / ![]() |
| PubMed 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. ...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. |
External links | Sci Adv / PubMed:42284399 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.9 - 7.9 Å |
| Structure data | ![]() EMDB-73226: HBV wildtype capsid with packaged E. coli RNA ![]() EMDB-73227: Focused map of HBV with BAY41-4109 ![]() EMDB-73229: Focused map of HBV Capsid with compound HAP12 |
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Hepatitis B virus
Homo sapiens (human)