Tolvaptan, an FDA-approved drug, inhibits Zika virus infection both in vitro and in vivo

doi:10.5246/jcps.2021.03.017

Abstract

Abstract:

As a previously neglected member of flavivirus, Zika virus (ZIKV) has recently emerged and caused a global health concern because of its link to microcephaly and other congenital defects. Currently, no anti-ZIKV vaccine or therapy is commercially available. In this drug-screening study, tolvaptan, an FDA-approved drug, was identified to possess the activity against ZIKV strains of Asian lineage with low cytotoxicity using plaque and MTT assays. The anti-ZIKV activity of tolvaptan was also demonstrated using virus yield reduction assay and Western blotting analysis. Time-of-drug-addition assay showed that tolvaptan exerted its anti-ZIKV activity between 6 and 14 h post-ZIKV inoculation, concurrent with the post-entry events of ZIKV life cycle. Tolvaptan also exhibited inhibitory effects on ZIKV strains of African lineage, indicating that its anti-ZIKV activity was not strain dependent. Notably, tolvaptan could also reduce ZIKV-induced mortality in infected mice. Overall, these results suggested that tolvaptan was a potential therapeutic candidate against ZIKV that is worth further evaluation.

Key words: Zika virus, Tolvaptan, Antiviral, Microcephaly, Flavivirus

Supporting:

Xiuxiu Chen, Ronghua Luo, Zhaiwen Yao, Changbo Zheng, Qiuju Tang, Wei Pang, Fang Wang, Liumeng Yang, Sidong Xiong, Yongtang Zheng. Tolvaptan, an FDA-approved drug, inhibits Zika virus infection both in vitro and in vivo[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(3): 218-229.

Figures/Tables 5

References 43

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