Repurposing of Doramectin as a New Anti-Zika Virus Agent
Zika virus (ZIKV), belonging to the <i>Flavivirus</i> 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 disc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/5/1068 |
| _version_ | 1797598128803676160 |
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| author | Yujia Zhu Minqi Liang Jianchen Yu Bingzhi Zhang Ge Zhu Yun Huang Zhenjian He Jie Yuan |
| author_facet | Yujia Zhu Minqi Liang Jianchen Yu Bingzhi Zhang Ge Zhu Yun Huang Zhenjian He Jie Yuan |
| author_sort | Yujia Zhu |
| collection | DOAJ |
| description | Zika virus (ZIKV), belonging to the <i>Flavivirus</i> 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 (EC<sub>50</sub> value from 0.85 μM to 3.00 μM) with low cytotoxicity (CC<sub>50</sub> > 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 (K<sub>d</sub> = 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. |
| first_indexed | 2024-03-11T03:14:58Z |
| format | Article |
| id | doaj.art-f6072263762f4c148ed1c427be0b7305 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T03:14:58Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f6072263762f4c148ed1c427be0b73052023-11-18T03:38:29ZengMDPI AGViruses1999-49152023-04-01155106810.3390/v15051068Repurposing of Doramectin as a New Anti-Zika Virus AgentYujia Zhu0Minqi Liang1Jianchen Yu2Bingzhi Zhang3Ge Zhu4Yun Huang5Zhenjian He6Jie Yuan7School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaSchool of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaSchool of Chemistry, South China Normal University, Guangzhou 510006, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaZhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, ChinaSchool of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaSchool of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaZika virus (ZIKV), belonging to the <i>Flavivirus</i> 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 (EC<sub>50</sub> value from 0.85 μM to 3.00 μM) with low cytotoxicity (CC<sub>50</sub> > 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 (K<sub>d</sub> = 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.https://www.mdpi.com/1999-4915/15/5/1068ZIKVdoramectinantiviral agentRdRp |
| spellingShingle | Yujia Zhu Minqi Liang Jianchen Yu Bingzhi Zhang Ge Zhu Yun Huang Zhenjian He Jie Yuan Repurposing of Doramectin as a New Anti-Zika Virus Agent Viruses ZIKV doramectin antiviral agent RdRp |
| title | Repurposing of Doramectin as a New Anti-Zika Virus Agent |
| title_full | Repurposing of Doramectin as a New Anti-Zika Virus Agent |
| title_fullStr | Repurposing of Doramectin as a New Anti-Zika Virus Agent |
| title_full_unstemmed | Repurposing of Doramectin as a New Anti-Zika Virus Agent |
| title_short | Repurposing of Doramectin as a New Anti-Zika Virus Agent |
| title_sort | repurposing of doramectin as a new anti zika virus agent |
| topic | ZIKV doramectin antiviral agent RdRp |
| url | https://www.mdpi.com/1999-4915/15/5/1068 |
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