Computational Approaches to Predict Hepatitis B Virus Capsid Protein Mutations That Confer Resistance to Capsid Assembly Modulators.

ABSTRACT: Capsid assembly modulators (CAMs) are a novel class of antiviral agents in clinical development for the treatment of chronic hepatitis B. CAMs inhibit hepatitis B virus (HBV) replication by binding to a hydrophobic pocket, i.e., HAP pocket, between HBV capsid protein (Cp) dimer-dimer interfaces to misdirect its assembly into empty capsids or aberrant structures and designated as CAM-E and CAM-A, respectively. Because the emergence of CAM-resistant variants results in the failure of antiviral therapy, it is important to rationally design CAMs with a high barrier of resistance for development. To establish computational approaches for the prediction of Cp mutations that confer resistance to CAMs, we investigated the interaction of representative CAM-A and CAM-E compounds, BAY 41-4109 and JNJ

SUBMITTER: Tolufashe G 

PROVIDER: S-EPMC11945318 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature