Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro
African swine fever virus (ASFV) infection is a major public and socioeconomic concern that has a serious impact on the global swine industry. Unfortunately, there are currently no commercially available vaccines or antiviral agents that are both safe and effective against ASFV. In the study, we use...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2220572 |
| _version_ | 1827211481755680768 |
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| author | Shibang Guo Yibo Zhang Zhankui Liu Daozhong Wang Hui Liu Liang Li Qichao Chen Dan Yang Qingyun Liu Huihui Guo Shuang Mou Huanchun Chen Xiangru Wang |
| author_facet | Shibang Guo Yibo Zhang Zhankui Liu Daozhong Wang Hui Liu Liang Li Qichao Chen Dan Yang Qingyun Liu Huihui Guo Shuang Mou Huanchun Chen Xiangru Wang |
| author_sort | Shibang Guo |
| collection | DOAJ |
| description | African swine fever virus (ASFV) infection is a major public and socioeconomic concern that has a serious impact on the global swine industry. Unfortunately, there are currently no commercially available vaccines or antiviral agents that are both safe and effective against ASFV. In the study, we use primary porcine alveolar macrophages to screen a kinase inhibitor library for anti-ASFV compounds. Six candidate compounds that inhibited ASFV infection with inhibition of > 90% were identified, among which brincidofovir exhibited optimal inhibitory effects on ASFV. Brincidofovir reduces ASFV replication in a dose-dependent manner (IC50 = 2.76 nM) without cytotoxicity (CC50 = 58 μM). It possesses the ability to reduce viral titres and inhibit viral structural protein expression. Time-of-addition assays suggest that the compound interferes with the post-invasion stage of the viral infection cycle. In pig challenge experiments, brincidofovir was indicated to protect pigs against ASFV-induced lethality by decreasing the viral load in organs and peripheral blood, while it alleviated the histopathological changes associated with ASFV infection. Furthermore, brincidofovir also decreased viral shedding in pigs with ASFV infection. Our data together demonstrate that brincidofovir may serve as a potentially effective agent for the prevention and control of ASFV infection, whereas further investigations are still required. |
| first_indexed | 2024-03-08T11:51:38Z |
| format | Article |
| id | doaj.art-a6a4dc3ccb5d4c6389dc55ec808394da |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2025-03-21T13:44:20Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-a6a4dc3ccb5d4c6389dc55ec808394da2024-06-26T10:39:27ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2220572Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitroShibang Guo0Yibo Zhang1Zhankui Liu2Daozhong Wang3Hui Liu4Liang Li5Qichao Chen6Dan Yang7Qingyun Liu8Huihui Guo9Shuang Mou10Huanchun Chen11Xiangru Wang12National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of ChinaAfrican swine fever virus (ASFV) infection is a major public and socioeconomic concern that has a serious impact on the global swine industry. Unfortunately, there are currently no commercially available vaccines or antiviral agents that are both safe and effective against ASFV. In the study, we use primary porcine alveolar macrophages to screen a kinase inhibitor library for anti-ASFV compounds. Six candidate compounds that inhibited ASFV infection with inhibition of > 90% were identified, among which brincidofovir exhibited optimal inhibitory effects on ASFV. Brincidofovir reduces ASFV replication in a dose-dependent manner (IC50 = 2.76 nM) without cytotoxicity (CC50 = 58 μM). It possesses the ability to reduce viral titres and inhibit viral structural protein expression. Time-of-addition assays suggest that the compound interferes with the post-invasion stage of the viral infection cycle. In pig challenge experiments, brincidofovir was indicated to protect pigs against ASFV-induced lethality by decreasing the viral load in organs and peripheral blood, while it alleviated the histopathological changes associated with ASFV infection. Furthermore, brincidofovir also decreased viral shedding in pigs with ASFV infection. Our data together demonstrate that brincidofovir may serve as a potentially effective agent for the prevention and control of ASFV infection, whereas further investigations are still required.https://www.tandfonline.com/doi/10.1080/22221751.2023.2220572African swine fever viruskinase inhibitor libraryantiviral activitybrincidofovirChinese Bama minipig |
| spellingShingle | Shibang Guo Yibo Zhang Zhankui Liu Daozhong Wang Hui Liu Liang Li Qichao Chen Dan Yang Qingyun Liu Huihui Guo Shuang Mou Huanchun Chen Xiangru Wang Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro Emerging Microbes and Infections African swine fever virus kinase inhibitor library antiviral activity brincidofovir Chinese Bama minipig |
| title | Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro |
| title_full | Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro |
| title_fullStr | Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro |
| title_full_unstemmed | Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro |
| title_short | Brincidofovir is a robust replication inhibitor against African swine fever virus in vivo and in vitro |
| title_sort | brincidofovir is a robust replication inhibitor against african swine fever virus in vivo and in vitro |
| topic | African swine fever virus kinase inhibitor library antiviral activity brincidofovir Chinese Bama minipig |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2220572 |
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