Müller Patrick, Downard Kevin M
Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Australia.
Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Australia.
J Pharm Biomed Anal. 2015;111:222-30. doi: 10.1016/j.jpba.2015.03.014. Epub 2015 Mar 24.
The molecular basis for the antiviral inhibitory properties of three catechins epigallocatechin gallate, epicatechin gallate and catechin-5-gallate derived from green tea was assessed in terms of their ability to interact with influenza neuraminidase. This was investigated using a molecular based MALDI mass spectrometry approach in conjunction with companion inhibition assays employing confocal microscopy. Together with computational molecular docking, all three catechins were found to bind to influenza neuraminidase in the vicinity of a structurally conserved cavity adjacent to residue 430 that has been suggested to be a secondary sialic acid binding site. In doing so, they were effective inhibitors of the enzyme preventing the release of progeny viruses from host cells at inhibitor concentrations (IC50 values) of between 100 and 173 μM. Importantly, their different binding profiles avoid the limitations of existing neuraminidase inhibitors manifested by the evolution of antiviral resistance strains.
从绿茶中提取的三种儿茶素（表没食子儿茶素没食子酸酯、表儿茶素没食子酸酯和儿茶素-5-没食子酸酯）的抗病毒抑制特性的分子基础，根据它们与流感神经氨酸酶相互作用的能力进行了评估。这是使用基于分子的基质辅助激光解吸电离质谱方法，并结合采用共聚焦显微镜的伴随抑制试验来进行研究的。与计算分子对接一起，发现所有三种儿茶素都在与430位残基相邻的结构保守腔附近结合到流感神经氨酸酶上，该腔被认为是一个二级唾液酸结合位点。这样做时，它们是该酶的有效抑制剂，在抑制剂浓度（IC50值）为100至173μM之间时可防止子代病毒从宿主细胞中释放。重要的是，它们不同的结合模式避免了现有神经氨酸酶抑制剂因抗病毒抗性菌株的进化而表现出的局限性。
