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Updated: May 9, 2026

Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Assembly-directed antivirals differentially bind quasiequivalent pockets to modify hepatitis B virus capsid tertiary
Sarah P Katen1, Zhenning Tan, Srinivas Reddy Chirapu
1Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USA.
Abstract:
Hepatitis B virus (HBV) is a major cause of liver disease. Assembly of the HBV capsid is a critical step in virus production and an attractive target for new antiviral therapies. We determined the structure of HBV capsid in complex with AT-130, a member of the phenylpropenamide family of assembly effectors. AT-130 causes tertiary and quaternary structural changes but does not disrupt capsid structure. AT-130 binds a hydrophobic pocket that also accommodates the previously characterized heteroaryldihydropyrimidine compounds but favors a unique quasiequivalent location on the capsid surface. Thus, this pocket is a promiscuous drug-binding site and a likely target for different assembly effectors with a broad range of mechanisms of activity. That AT-130 successfully decreases virus production by increasing capsid assembly rate without disrupting capsid structure delineates a paradigm in antiviral design, that disrupting reaction timing is a viable strategy for assembly effectors of HBV and other viruses.
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