A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase
The Zika virus (ZIKV) is a mosquito-borne virus that already poses a danger to worldwide human health. Patients infected with ZIKV generally have mild symptoms like a low-grade fever and joint pain. However, severe symptoms can also occur, such as Guillain-Barré syndrome, neuropathy, and myelitis. P...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/5/978 |
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| author | Kexin Zhang Jingyao Liang Bingzhi Zhang Lishan Huang Jianchen Yu Xuhan Xiao Zhenjian He Huaming Tao Jie Yuan |
| author_facet | Kexin Zhang Jingyao Liang Bingzhi Zhang Lishan Huang Jianchen Yu Xuhan Xiao Zhenjian He Huaming Tao Jie Yuan |
| author_sort | Kexin Zhang |
| collection | DOAJ |
| description | The Zika virus (ZIKV) is a mosquito-borne virus that already poses a danger to worldwide human health. Patients infected with ZIKV generally have mild symptoms like a low-grade fever and joint pain. However, severe symptoms can also occur, such as Guillain-Barré syndrome, neuropathy, and myelitis. Pregnant women infected with ZIKV may also cause microcephaly in newborns. To date, we still lack conventional antiviral drugs to treat ZIKV infections. Marine natural products have novel structures and diverse biological activities. They have been discovered to have antibacterial, antiviral, anticancer, and other therapeutic effects. Therefore, marine products are important resources for compounds for innovative medicines. In this study, we identified a marine natural product, harzianopyridone (HAR), that could inhibit ZIKV replication with EC<sub>50</sub> values from 0.46 to 2.63 µM while not showing obvious cytotoxicity in multiple cellular models (CC<sub>50</sub> > 45 µM). Further, it also reduced the expression of viral proteins and protected cells from viral infection. More importantly, we found that HAR directly bound to the ZIKV RNA-dependent RNA polymerase (RdRp) and suppressed its polymerase activity. Collectively, our findings provide HAR as an option for the development of anti-ZIKV drugs. |
| first_indexed | 2024-04-25T00:24:06Z |
| format | Article |
| id | doaj.art-255e14b89a964a74b9c4c0f894b1f61b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-25T00:24:06Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-255e14b89a964a74b9c4c0f894b1f61b2024-03-12T16:50:37ZengMDPI AGMolecules1420-30492024-02-0129597810.3390/molecules29050978A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA PolymeraseKexin Zhang0Jingyao Liang1Bingzhi Zhang2Lishan Huang3Jianchen Yu4Xuhan Xiao5Zhenjian He6Huaming Tao7Jie Yuan8School of Public Health, Sun Yat-sen University, Guangzhou 510080, 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, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaSchool of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, ChinaKey Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, ChinaThe Zika virus (ZIKV) is a mosquito-borne virus that already poses a danger to worldwide human health. Patients infected with ZIKV generally have mild symptoms like a low-grade fever and joint pain. However, severe symptoms can also occur, such as Guillain-Barré syndrome, neuropathy, and myelitis. Pregnant women infected with ZIKV may also cause microcephaly in newborns. To date, we still lack conventional antiviral drugs to treat ZIKV infections. Marine natural products have novel structures and diverse biological activities. They have been discovered to have antibacterial, antiviral, anticancer, and other therapeutic effects. Therefore, marine products are important resources for compounds for innovative medicines. In this study, we identified a marine natural product, harzianopyridone (HAR), that could inhibit ZIKV replication with EC<sub>50</sub> values from 0.46 to 2.63 µM while not showing obvious cytotoxicity in multiple cellular models (CC<sub>50</sub> > 45 µM). Further, it also reduced the expression of viral proteins and protected cells from viral infection. More importantly, we found that HAR directly bound to the ZIKV RNA-dependent RNA polymerase (RdRp) and suppressed its polymerase activity. Collectively, our findings provide HAR as an option for the development of anti-ZIKV drugs.https://www.mdpi.com/1420-3049/29/5/978harzianopyridoneZIKVmarine natural productsantiviral drugsRdRp |
| spellingShingle | Kexin Zhang Jingyao Liang Bingzhi Zhang Lishan Huang Jianchen Yu Xuhan Xiao Zhenjian He Huaming Tao Jie Yuan A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase Molecules harzianopyridone ZIKV marine natural products antiviral drugs RdRp |
| title | A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase |
| title_full | A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase |
| title_fullStr | A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase |
| title_full_unstemmed | A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase |
| title_short | A Marine Natural Product, Harzianopyridone, as an Anti-ZIKV Agent by Targeting RNA-Dependent RNA Polymerase |
| title_sort | marine natural product harzianopyridone as an anti zikv agent by targeting rna dependent rna polymerase |
| topic | harzianopyridone ZIKV marine natural products antiviral drugs RdRp |
| url | https://www.mdpi.com/1420-3049/29/5/978 |
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