Anti‐HBV Activities of Cembranoids from the South China Sea Soft Coral Sinularia pedunculata and Their Structure Activity Relationship

Abstract

Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. In previous studies, it has been demonstrated that cembranoid‐type diterpenoids showed significant anti‐inflammatory and anti‐colorectal cancer activities. In this study, cembranoids isolated from Sinularia pedunculata was found with anti‐HBV activity for the first time. Among them, compound 6 showed significant anti‐HBV activity with an IC50 value of 5.57 µM without cytotoxicity. We analysed the preliminary structure‐activity relationship (SAR). Furthermore, it is demonstrated that compound 6 can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti‐HBV activity in HepG2‐NTCP infection system. Finally, we find the anti‐HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter.