Mechanistic insights into CAM-induced disruption of HBV capsids revealed by all-atom MD simulations.

ABSTRACT: Capsid assembly modulators (CAMs) represent a promising antiviral strategy against hepatitis B virus (HBV), but their effects on pre-formed capsids remain incompletely understood. Here, all-atom molecular dynamics (MD) simulations of intact HBV capsids complexed with prototypical CAM-As (HAP1, HAP18) and CAM-Es (AT130), reveal how structural changes induced by small molecule binding in the interdimer interfaces propagate through the shell lattice to yield global morphological consequences. Each quasi-equivalent interface exhibits a unique response: A sites, located within the pentameric capsomers, are unfilled in these systems and altered marginally by the presence of CAMs in neighboring interfaces. B sites are the most open and "CAM-ready," suggesting uptake requires minimal conformationa

SUBMITTER: Perez-Segura C 

PROVIDER: S-EPMC12904591 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature