College of Veterinary Medicine, South China Agricultural UniversityKey Laboratory for Animal Vaccine Development, Ministry of AgricultureInstitute of Laboratory Animal, Jinan University GuangzhouCollege of Pharmacy, Jinan UniversityGuangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, China.
Influenza Other Respir Viruses. 2013 Nov;7(6):922-31. doi: 10.1111/irv.12035. Epub 2012 Nov 8.
Few drugs are currently licensed to treat influenza A infection, and new therapies are needed, especially for highly pathogenic strains. Traditional medicinal plants, such as Lycoris radiata, are a potential source of new antiviral agents.
To test 15 Amaryllidaceae alkaloids isolated from the bulbs of L. radiata in vitro for antiviral activities against influenza virus type A, A/Chicken/GuangDong/178/2004 (H5N1, 178).
Antiviral activities of the compounds were tested in time-of-addition assays, hemagglutination inhibition (HI) assays, neuraminidase (NA) activity assays, and viral entry inhibition assays using H5N1-HIV pseudoviruses. Effects of the compounds on localization and activity of the viral ribonucleoprotein (RNP) were determined by immunofluorescence and an RNP minigenome assay, respectively.
Among the alkaloids, lycorine (AA1), hippeastrine (AA2), hemanthamine (AA3) and 11-hydroxy vittatine (AA4) exhibited antiviral activities, with EC90 values of 0·52, 82·07, 4·15, and 13·45 μm, respectively. These compounds did not affect the function of the outer membrane proteins or the viral entry process and viral RNP activity. As AA1 and AA3 exhibited stronger antiviral activities, they were further analyzed. Intracellular nucleoprotein (NP) localization showed that AA1 and AA3 inhibited the RNP complex in the nucleus at an early stage of a single-round and multi-round of replication.
Four Amaryllidaceae alkaloids were first determined that could exert anti-influenza activities after virus entry into cells. Furthermore, AA1 and AA3 could inhibit nuclear-to-cytoplasmic export of the RNP complex of virus replication. Thus, these compounds may be developed further as anti-influenza drug candidates.
目前仅有少数药物被许可用于治疗甲型流感感染，因此需要新的治疗方法，尤其是针对高致病性菌株。传统药用植物，如石蒜，是新型抗病毒药物的潜在来源。
在体外测试从石蒜鳞茎中分离得到的 15 种石蒜科生物碱对甲型流感病毒 A/鸡/广东/178/2004（H5N1，178）株的抗病毒活性。
通过时间添加测定、血凝抑制（HI）测定、神经氨酸酶（NA）活性测定以及使用 H5N1-HIV 假病毒的病毒进入抑制测定，测试化合物的抗病毒活性。通过免疫荧光和 RNP 小基因测定，分别确定化合物对病毒核糖核蛋白（RNP）的定位和活性的影响。
在所测试的生物碱中，石蒜碱（AA1）、海葱碱（AA2）、海罂粟碱（AA3）和 11-羟基紫堇碱（AA4）表现出抗病毒活性，EC90 值分别为 0.52、82.07、4.15 和 13.45 μm。这些化合物不影响外膜蛋白的功能或病毒进入过程和病毒 RNP 活性。由于 AA1 和 AA3 表现出更强的抗病毒活性，因此进一步对它们进行了分析。细胞内核蛋白（NP）定位显示，AA1 和 AA3 在单轮和多轮复制的早期阶段抑制了核内 RNP 复合物。
首次确定了 4 种石蒜科生物碱可在病毒进入细胞后发挥抗流感活性。此外，AA1 和 AA3 可抑制病毒复制中 RNP 复合物的核质输出。因此，这些化合物可能进一步开发为抗流感药物候选物。
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