Anti-flavivirus activity of polyoxometalate

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.