Hossan Md Shahadat, Fatima Ayesha, Rahmatullah Mohammed, Khoo Teng Jin, Nissapatorn Veeranoot, Galochkina Anastasia V, Slita Alexander V, Shtro Anna A, Nikolaeva Yulia, Zarubaev Vladimir V, Wiart Christophe
School of Pharmacy, University of Nottingham, Malaysia Campus, 43500, Semenyih, Malaysia.
Faculty of Pharmacy, Quest International University, 30250, Ipoh, Malaysia.
Arch Virol. 2018 Aug;163(8):2121-2131. doi: 10.1007/s00705-018-3842-6. Epub 2018 Apr 10.
Viral respiratory infections are raising serious concern globally. Asian medicinal plants could be useful in improving the current treatment strategies for influenza. The present study examines the activity of five plants from Bangladesh against influenza virus. MDCK cells infected with influenza virus A/Puerto Rico/8/34 (H1N1) were treated with increasing concentrations of ethyl acetate extracts, and their cytotoxicity (CC), virus-inhibiting activity (IC), and selectivity index (SI) were calculated. The ethyl acetate extract of fruits of Embelia ribes Burm. f. (Myrsinaceae) had the highest antiviral activity, with an IC of 0.2 µg/mL and a SI of 32. Its major constituent, embelin, was further isolated and tested against the same virus. Embelin demonstrated antiviral activity, with an IC of 0.3 µM and an SI of 10. Time-of-addition experiments revealed that embelin was most effective when added at early stages of the viral life cycle (0-1 h postinfection). Embelin was further evaluated against a panel of influenza viruses including influenza A and B viruses that were susceptible or resistant to rimantadine and oseltamivir. Among the viruses tested, avian influenza virus A/mallard/Pennsylvania/10218/84 (H5N2) was the most susceptible to embelin (SI = 31), while A/Aichi/2/68 (H3N2) virus was the most resistant (SI = 5). In silico molecular docking showed that the binding site for embelin is located in the receptor-binding domain of the viral hemagglutinin. The results of this study provide evidence that E. ribes can be used for development of a novel alternative anti-influenza plant-based agent.
病毒性呼吸道感染正在全球引起严重关注。亚洲药用植物可能有助于改进当前的流感治疗策略。本研究检测了来自孟加拉国的五种植物对流感病毒的活性。用浓度递增的乙酸乙酯提取物处理感染甲型流感病毒A/波多黎各/8/34（H1N1）的MDCK细胞，并计算其细胞毒性（CC）、病毒抑制活性（IC）和选择性指数（SI）。余甘子（紫金牛科）果实的乙酸乙酯提取物具有最高的抗病毒活性，IC为0.2μg/mL，SI为32。进一步分离了其主要成分余甘子醌，并针对同一病毒进行测试。余甘子醌表现出抗病毒活性，IC为0.3μM，SI为10。加样时间实验表明，余甘子醌在病毒生命周期早期（感染后0 - 1小时）添加时最为有效。余甘子醌还针对一组流感病毒进行了评估，这些病毒包括对金刚烷胺和奥司他韦敏感或耐药的甲型和乙型流感病毒。在所测试的病毒中，禽流感病毒A/野鸭/宾夕法尼亚/10218/84（H5N2）对余甘子醌最敏感（SI = 31），而A/爱知/2/68（H3N2）病毒最耐药（SI = 5）。计算机模拟分子对接显示，余甘子醌的结合位点位于病毒血凝素的受体结合结构域。本研究结果提供了证据，表明余甘子可用于开发一种新型的基于植物的抗流感替代药物。
