2. Academic Validation
  3. Repurposing of Doramectin as a New Anti-Zika Virus Agent

Repurposing of Doramectin as a New Anti-Zika Virus Agent

  • Viruses. 2023 Apr 27;15(5):1068. doi: 10.3390/v15051068.
Yujia Zhu 1 2,  Minqi Liang 1 2,  Jianchen Yu 3 4,  Bingzhi Zhang 5,  Ge Zhu 4,  Yun Huang 6,  Zhenjian He 1 2,  Jie Yuan 2 4
Affiliations

Affiliations

  • 1 School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
  • 2 Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
  • 3 School of Chemistry, South China Normal University, Guangzhou 510006, China.
  • 4 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
  • 5 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 6 School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
PMID: 37243154 DOI: 10.3390/v15051068
Abstract

Zika virus (ZIKV), belonging to the Flavivirus family and mainly transmitted by mosquitoes, causes a variety of adverse outcomes, including Guillain-Barré syndrome, microcephaly, and meningoencephalitis. However, there are no approved vaccines or drugs available for ZIKV. The discovery and research on drugs for ZIKV are still essential. In this study, we identified doramectin, an approved veterinary antiparasitic drug, as a novel anti-ZIKV agent (EC50 value from 0.85 μM to 3.00 μM) with low cytotoxicity (CC50 > 50 μM) in multiple cellular models. The expression of ZIKV proteins also decreased significantly under the treatment of doramectin. Further study showed that doramectin directly interacted with the key enzyme for ZIKV genome replication, RNA-dependent RNA polymerase (RdRp), with a stronger affinity (Kd = 16.9 μM), which may be related to the effect on ZIKV replication. These results suggested that doramectin might serve as a promising drug candidate for anti-ZIKV.

Keywords

RdRp; ZIKV; antiviral agent; doramectin.

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