Department of Biosystems and Biotechnology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
Antiviral Res. 2013 Oct;100(1):75-83. doi: 10.1016/j.antiviral.2013.07.009. Epub 2013 Jul 25.
Human gammaherpesviruses including Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are important pathogens as they persist in the host and cause various malignancies. However, few antiviral drugs are available to efficiently control gammaherpesvirus replication. Here we identified the antiviral activity of angelicin against murine gammaherpesvirus 68 (MHV-68), genetically and biologically related to human gammaherpesviruses. Angelicin, a furocoumarin naturally occurring tricyclic aromatic compound, efficiently inhibited lytic replication of MHV-68 in a dose-dependent manner following the virus entry. The IC50 of angelicin antiviral activity was estimated to be 28.95μM, while the CC50 of angelicin was higher than 2600μM. Furthermore, incubation with angelicin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lytic replication of human gammaherpresviruses in both EBV- and KSHV-infected cells. Taken together, these results suggest that MHV-68 can be a useful tool to screen novel antiviral agents against human gammaherepsviruses and that angelicin may provide a lead structure for the development of antiviral drug against gammaherpesviruses.
人γ疱疹病毒包括 EBV 和卡波氏肉瘤相关疱疹病毒（KSHV）是重要的病原体，因为它们在宿主中持续存在并导致各种恶性肿瘤。然而，目前可用的抗疱疹病毒药物很少能够有效地控制γ疱疹病毒的复制。在这里，我们发现了白芷素对鼠γ疱疹病毒 68（MHV-68）的抗病毒活性，MHV-68 在遗传和生物学上与人γ疱疹病毒有关。白芷素是一种天然存在的三环芳香族化合物呋喃香豆素，能够以剂量依赖的方式在病毒进入后有效抑制 MHV-68 的裂解复制。白芷素抗病毒活性的 IC50 估计为 28.95μM，而白芷素的 CC50 高于 2600μM。此外，用白芷素孵育能够有效地抑制 TPA 诱导的 EBV 和 KSHV 感染细胞中的人γ疱疹病毒裂解复制。综上所述，这些结果表明 MHV-68 可以作为筛选针对人γ疱疹病毒的新型抗病毒药物的有用工具，而白芷素可能为开发针对γ疱疹病毒的抗病毒药物提供一个先导结构。
