Department of Hepatology, First Hospital, Jilin University, Changchun, Jilin, 130021, China.
CAS Key Laboratory of Molecular Virology and Immunology, Unit of Viral Hepatitis, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; Shanghai Tech University, Shanghai, 201210, China.
Antiviral Res. 2020 Jul;179:104813. doi: 10.1016/j.antiviral.2020.104813. Epub 2020 May 4.
Viruses in the Flaviviridae family such as Zika virus (ZIKV), dengue virus (DENV), and Japanese encephalitis virus (JEV) are major public health concerns. The development of antiviral agents against these viruses is urgently needed. We have previously discovered that the Keggin structured polyoxometalate POM-12 has potent inhibitory activity against hepatitis C virus, another member of the Flaviviridae family. In this study, we tested its antiviral activity of DENV, JEV and ZIKV, and found that POM-12 dramatically inhibited their infection with IC50 value of 1.16 μM, 1.9 μM and 0.64 μM, respectively. Mechanistic studies indicated that POM-12 directly disrupted the integrity of these virions. Moreover, POM-12 also targeted the post-entry steps of viral replication of JEV, but having no similar activities on ZIKV and DENV. The differential actions of POM-12 on these viruses suggest that surface topology and charge of virion may have influence on its drug effect, and thus POM-12 may be modified to more efficiently inhibit these and other similar viruses.
黄病毒科（Flaviviridae）中的病毒，如 Zika 病毒（ZIKV）、登革热病毒（DENV）和日本脑炎病毒（JEV），是主要的公共卫生关注点。迫切需要开发针对这些病毒的抗病毒药物。我们之前发现，Keggin 结构的多金属氧酸盐 POM-12 对丙型肝炎病毒（Flaviviridae 家族的另一个成员）具有很强的抑制活性。在这项研究中，我们测试了 POM-12 对 DENV、JEV 和 ZIKV 的抗病毒活性，发现 POM-12 分别以 1.16 μM、1.9 μM 和 0.64 μM 的 IC50 值显著抑制了它们的感染。机制研究表明，POM-12 直接破坏了这些病毒粒子的完整性。此外，POM-12 还靶向 JEV 病毒复制的进入后步骤，但对 ZIKV 和 DENV 没有类似的作用。POM-12 对这些病毒的不同作用表明，病毒粒子的表面拓扑和电荷可能会影响其药物效果，因此可以对 POM-12 进行修饰，以更有效地抑制这些和其他类似的病毒。
