体外实验及计算分析揭示丹参酮IIA对甲型流感病毒的潜在抑制作用。
In vitro and computational insights revealing the potential inhibitory effect of Tanshinone IIA against influenza A virus.
作者信息
Elebeedy Dalia, Badawy Ingy, Elmaaty Ayman Abo, Saleh Moustafa M, Kandeil Ahmed, Ghanem Aml, Kutkat Omnia, Alnajjar Radwan, Abd El Maksoud Ahmed I, Al-Karmalawy Ahmed A
机构信息
College of Biotechnology, Misr University for Science and Technology (MUST), 6th of October City, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University, Port Said, 42526, Egypt.
出版信息
Comput Biol Med. 2022 Feb;141:105149. doi: 10.1016/j.compbiomed.2021.105149. Epub 2021 Dec 17.
Seasonal human influenza is a serious respiratory infection caused by influenza viruses that can be found all over the world. Type A influenza is a contagious viral infection that, if left untreated, can lead to life-threatening consequences. Fortunately, the plant kingdom has many potent medicines with broad-spectrum antiviral activity. Herein, six plant constituents, namely Tanshinone IIA 1, Carnosic acid 2, Rosmarinic acid 3, Glycyrrhetinic acid 4, Baicalein 5, and Salvianolic acid B 6, were screened for their antiviral activities against H1N1 virus using in vitro and in silico approaches. Hence, their anti-influenza activities were tested in vitro to determine inhibitory concentration 50 (IC) values after measuring their CC values using MTT assay on MDCK cells. Interestingly, Tanshinone IIA (TAN) 1 was the most promising member with CC = 9.678 μg/ml. Moreover, the plaque reduction assay carried on TAN 1 revealed promising viral inhibition percentages of 97.9%, 95.8%, 94.4%, and 91.7% using concentrations 0.05 μg/μl, 0.025 μg/μl, 0.0125 μg/μl, and 0.006 μg/μl, respectively. Furthermore, in silico molecular docking disclosed the superior affinities of Salvianolic acid B (SAL) 6 towards both surface glycoproteins of influenza A virus (namely, hemagglutinin (HA) and neuraminidase (NA)). The docked complexes of both SAL and TAN inside HA and NA receptor pockets were selected for 100 ns MD simulations followed by MM-GBSA binding free energy calculation to confirm the docking results and give more insights regarding the stability of both compounds inside influenza mentioned receptors, respectively. The selection criteria of the previously mentioned complexes were based on the fact that SAL showed the highest docking scores on both viral HA and NA glycoproteins whereas TAN achieved the best inhibitory activity on the other hand. Finally, we urge more advanced preclinical and clinical research, particularly for TAN, which could be used to treat the human influenza A virus effectively.
季节性人类流感是一种由流感病毒引起的严重呼吸道感染,这种病毒在世界各地都能发现。甲型流感是一种具有传染性的病毒感染,如果不加以治疗,可能会导致危及生命的后果。幸运的是,植物界有许多具有广谱抗病毒活性的有效药物。在此,使用体外和计算机模拟方法筛选了六种植物成分,即丹参酮IIA 1、鼠尾草酸2、迷迭香酸3、甘草次酸4、黄芩苷5和丹酚酸B 6,以检测它们对H1N1病毒的抗病毒活性。因此,在使用MTT法在MDCK细胞上测量它们的CC值后,在体外测试它们的抗流感活性以确定半数抑制浓度(IC)值。有趣的是,丹参酮IIA(TAN)1是最有前景的成分,CC = 9.678μg/ml。此外,对TAN 1进行的蚀斑减少试验显示,使用浓度分别为0.05μg/μl、0.025μg/μl、0.0125μg/μl和0.006μg/μl时,病毒抑制率分别为97.9%、95.8%、94.4%和91.7%,前景良好。此外,计算机模拟分子对接揭示了丹酚酸B(SAL)6对甲型流感病毒的两种表面糖蛋白(即血凝素(HA)和神经氨酸酶(NA))具有更高的亲和力。选择SAL和TAN在HA和NA受体口袋内的对接复合物进行100 ns的分子动力学模拟,然后进行MM-GBSA结合自由能计算,以分别确认对接结果并深入了解这两种化合物在流感相关受体内部的稳定性。上述复合物的选择标准基于这样一个事实,即SAL在病毒HA和NA糖蛋白上均显示出最高的对接分数,而TAN则具有最佳的抑制活性。最后,我们敦促开展更先进的临床前和临床研究,特别是针对TAN的研究,它可有效用于治疗人类甲型流感病毒。