State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Viruses. 2023 Mar 6;15(3):688. doi: 10.3390/v15030688.
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 , 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 , 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.
猪繁殖与呼吸综合征病毒（PRRSV）是引起猪繁殖与呼吸综合征（PRRS）的病原体，在全球范围内广泛流行，给全球养猪业造成了巨大的经济损失。虽然目前的商业疫苗未能有效控制 PRRS，但迫切需要开发针对 PRRSV 的安全有效的抗病毒药物。生物碱是具有广泛药理和生物学活性的天然产物。本文研究了一种存在于多种植物中的苯并菲啶生物碱血根碱，发现其是 PRRSV 的有效拮抗剂。血根碱通过靶向病毒生命周期的内化、复制和释放阶段来抑制 PRRSV 的增殖。此外，通过网络药理学和分子对接发现，ALB、AR、MAPK8、MAPK14、IGF1、GSK3B、PTGS2 和 NOS2 是与血根碱抗 PRRSV 作用相关的潜在关键靶点。值得注意的是，我们还证明了血根碱与白屈菜红碱（另一种来源于白屈菜的关键生物活性生物碱）联合使用可以提高抗病毒活性。综上所述，本研究结果表明血根碱作为一种新型抗 PRRSV 药物的候选物具有很大的潜力。
