Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition Mechanisms
Porcine reproductive and respiratory syndrome virus (PRRSV), the etiological agent of PRRS, is prevalent worldwide, causing substantial and immense economic losses to the global swine industry. While current commercial vaccines fail to efficiently control PRRS, the development of safe and effective...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/3/688 |
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| author | Qiyun Ke Kaiqi Duan Yan Cheng Si Xu Shaobo Xiao Liurong Fang |
| author_facet | Qiyun Ke Kaiqi Duan Yan Cheng Si Xu Shaobo Xiao Liurong Fang |
| author_sort | Qiyun Ke |
| collection | DOAJ |
| description | Porcine reproductive and respiratory syndrome virus (PRRSV), the etiological agent of PRRS, is prevalent worldwide, causing substantial and immense economic losses to the global swine industry. While current commercial vaccines fail to efficiently control PRRS, the development of safe and effective antiviral drugs against PRRSV is urgently required. Alkaloids are natural products with wide pharmacological and biological activities. Herein, sanguinarine, a benzophenanthridine alkaloid that occurs in many plants such as <i>Macleaya cordata</i>, was demonstrated as a potent antagonist of PRRSV. Sanguinarine attenuated PRRSV proliferation by targeting the internalization, replication, and release stages of the viral life cycle. Furthermore, ALB, AR, MAPK8, MAPK14, IGF1, GSK3B, PTGS2, and NOS2 were found as potential key targets related to the anti-PRRSV effect of sanguinarine as revealed by network pharmacology and molecular docking. Significantly, we demonstrated that the combination of sanguinarine with chelerythrine, another key bioactive alkaloid derived from <i>Macleaya cordata</i>, improved the antiviral activity. In summary, our findings reveal the promising potential of sanguinarine as a novel candidate for the development of anti-PRRSV agents. |
| first_indexed | 2024-03-11T05:47:28Z |
| format | Article |
| id | doaj.art-bfed0154b20f40b28a2ba984cc3aeeff |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T05:47:28Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-bfed0154b20f40b28a2ba984cc3aeeff2023-11-17T14:22:56ZengMDPI AGViruses1999-49152023-03-0115368810.3390/v15030688Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition MechanismsQiyun Ke0Kaiqi Duan1Yan Cheng2Si Xu3Shaobo Xiao4Liurong Fang5State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaPorcine reproductive and respiratory syndrome virus (PRRSV), the etiological agent of PRRS, is prevalent worldwide, causing substantial and immense economic losses to the global swine industry. While current commercial vaccines fail to efficiently control PRRS, the development of safe and effective antiviral drugs against PRRSV is urgently required. Alkaloids are natural products with wide pharmacological and biological activities. Herein, sanguinarine, a benzophenanthridine alkaloid that occurs in many plants such as <i>Macleaya cordata</i>, was demonstrated as a potent antagonist of PRRSV. Sanguinarine attenuated PRRSV proliferation by targeting the internalization, replication, and release stages of the viral life cycle. Furthermore, ALB, AR, MAPK8, MAPK14, IGF1, GSK3B, PTGS2, and NOS2 were found as potential key targets related to the anti-PRRSV effect of sanguinarine as revealed by network pharmacology and molecular docking. Significantly, we demonstrated that the combination of sanguinarine with chelerythrine, another key bioactive alkaloid derived from <i>Macleaya cordata</i>, improved the antiviral activity. In summary, our findings reveal the promising potential of sanguinarine as a novel candidate for the development of anti-PRRSV agents.https://www.mdpi.com/1999-4915/15/3/688porcine reproductive and respiratory syndrome virus (PRRSV)sanguinarineantiviralalkaloidtarget |
| spellingShingle | Qiyun Ke Kaiqi Duan Yan Cheng Si Xu Shaobo Xiao Liurong Fang Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition Mechanisms Viruses porcine reproductive and respiratory syndrome virus (PRRSV) sanguinarine antiviral alkaloid target |
| title | Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition Mechanisms |
| title_full | Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition Mechanisms |
| title_fullStr | Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition Mechanisms |
| title_full_unstemmed | Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition Mechanisms |
| title_short | Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition Mechanisms |
| title_sort | sanguinarine exhibits antiviral activity against porcine reproductive and respiratory syndrome virus via multisite inhibition mechanisms |
| topic | porcine reproductive and respiratory syndrome virus (PRRSV) sanguinarine antiviral alkaloid target |
| url | https://www.mdpi.com/1999-4915/15/3/688 |
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