Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles
Zika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profil...
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| Format: | Article |
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2174777 |
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| author | Nailou Zhang Zhongyuan Tan Jinbo Wei Sai Zhang Yan Liu Yuanjiu Miao Qingwen Ding Wenfu Yi Min Gan Chunjie Li Bin Liu Hanzhong Wang Zhenhua Zheng |
| author_facet | Nailou Zhang Zhongyuan Tan Jinbo Wei Sai Zhang Yan Liu Yuanjiu Miao Qingwen Ding Wenfu Yi Min Gan Chunjie Li Bin Liu Hanzhong Wang Zhenhua Zheng |
| author_sort | Nailou Zhang |
| collection | DOAJ |
| description | Zika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future. |
| format | Article |
| id | doaj-art-9efaac8c64e940cdb97d2d5431ae857c |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-9efaac8c64e940cdb97d2d5431ae857c2025-08-20T01:49:16ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112110.1080/22221751.2023.2174777Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profilesNailou Zhang0Zhongyuan Tan1Jinbo Wei2Sai Zhang3Yan Liu4Yuanjiu Miao5Qingwen Ding6Wenfu Yi7Min Gan8Chunjie Li9Bin Liu10Hanzhong Wang11Zhenhua Zheng12CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaThe Joint Laboratory for Translational Precision Medicine, a. Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China and b. Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, People's Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCharacteristic Medical Center of Chinese People’s Armed Police Forces, Tianjin, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People’s Republic of ChinaZika virus (ZIKV) infections are typically asymptomatic but cause severe neurological complications (e.g. Guillain–Barré syndrome in adults, and microcephaly in newborns). There are currently no specific therapy or vaccine options available to prevent ZIKV infections. Temporal gene expression profiles of ZIKV-infected human brain microvascular endothelial cells (HBMECs) were used in this study to identify genes essential for viral replication. These genes were then used to identify novel anti-ZIKV agents and validated in publicly available data and functional wet-lab experiments. Here, we found that ZIKV effectively evaded activation of immune response-related genes and completely reprogrammed cellular transcriptional architectures. Knockdown of genes, which gradually upregulated during viral infection but showed distinct expression patterns between ZIKV- and mock infection, discovered novel proviral and antiviral factors. One-third of the 74 drugs found through signature-based drug repositioning and cross-reference with the Drug Gene Interaction Database (DGIdb) were known anti-ZIKV agents. In cellular assays, two promising antiviral candidates (Luminespib/NVP-AUY922, L-161982) were found to reduce viral replication without causing cell toxicity. Overall, our time-series transcriptome-based methods offer a novel and feasible strategy for antiviral drug discovery. Our strategies, which combine conventional and data-driven analysis, can be extended for other pathogens causing pandemics in the future.https://www.tandfonline.com/doi/10.1080/22221751.2023.2174777ZIKVtemporal transcriptomedrug repurposingantiviralsviral infection mechanisms |
| spellingShingle | Nailou Zhang Zhongyuan Tan Jinbo Wei Sai Zhang Yan Liu Yuanjiu Miao Qingwen Ding Wenfu Yi Min Gan Chunjie Li Bin Liu Hanzhong Wang Zhenhua Zheng Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles Emerging Microbes and Infections ZIKV temporal transcriptome drug repurposing antivirals viral infection mechanisms |
| title | Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles |
| title_full | Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles |
| title_fullStr | Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles |
| title_full_unstemmed | Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles |
| title_short | Identification of novel anti-ZIKV drugs from viral-infection temporal gene expression profiles |
| title_sort | identification of novel anti zikv drugs from viral infection temporal gene expression profiles |
| topic | ZIKV temporal transcriptome drug repurposing antivirals viral infection mechanisms |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2174777 |
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