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Updated: Jul 7, 2026

Alternative In Vitro Methods for the Determination of Viral Capsid Structural Integrity
Published on: November 16, 2017
Design, Synthesis, and Biological Evaluation of Highly Potent Boronic Acid (Boronate Ester)-Bearing
Yu Jin1, Yang Sun2, Shujie Zhao1
1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Jinan, Shandong, P. R. China.
Abstract:
Hepatitis B virus (HBV) capsid assembly modulators (CAMs) are a new class of specific antiviral agents that interfere with the capsid assembly process to exert antiviral effects. In this study, we rationally designed and chemically synthesized a series of novel boronic acid (boronate ester)-bearing heteroaryldihydropyrimidine (HAP) derivatives based on a multisite-binding strategy in the solvent-exposed region. Among them, CAB7-3 exhibited significant anti-HBV activity in HBV-integrated HepDES19 (EC50 = 0.07 μM), HepAD38 (EC50 = 0.001 μM) and HBV-infected HLCZ01 cells (EC50 = 0.002 μM), respectively. Additionally, CAB7-3 effectively reduced the level of HBV core protein (Cp) and repressed HBV replication in HBV carrier mice. Preliminary drug-likeness evaluation indicated that CAB7-3 displayed improved water solubility, superior microsomal metabolic stability in liver (T1/2 = 169.0 min) and lower hERG cardiotoxicity (IC50 = 6.5375 μM) compared to GLS4. All data demonstrated that CAB7-3 may be used as a potential candidate for further drug development.
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