Department of Central Lab, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
Clinical Laboratory, Liaocheng People's Hospital of Taishan Medical University, Liaocheng, Shandong, China.
Microbiol Immunol. 2020 Mar;64(3):189-201. doi: 10.1111/1348-0421.12763. Epub 2020 Jan 14.
Enterovirus 71 (EV71) is the predominant pathogen for severe hand, foot, and mouth disease (HFMD) in children younger than 5 years, and currently no effective drugs are available for EV71. Thus, there is an urgent need to develop new drugs for the control of EV71 infection. In this study, LJ04 was extracted from Laminaria japonica using diethylaminoethyl cellulose-52 with 0.4 mol/l NaCl as the eluent, and its virucidal activity was evaluated based on its cytopathic effects on a microplate. LJ04 is composed of fucose, galactose, and mannose and mainly showed good virucidal activity against EV71. The antiviral mechanisms of LJ04 were the direct inactivation of the virus, the blockage of virus binding, disruptions to viral entry, and weak inhibitory activity against the nonstructural protein 3C. The two most important findings from this study were that LJ04 inhibited EV71 proliferation in HM1900 cells, which are a human microglia cell line, and that LJ04 can directly inactivate EV71 within 2 hr at 37°C. This study demonstrates for the first time the ability of a polysaccharide from L. japonica to inhibit viral and 3C activity; importantly, the inhibition of 3C might have a minor effect on the antiviral effect of LJ04. Consequently, our results identify LJ04 as a potential drug candidate for the control of severe EV71 infection in clinical settings.
肠道病毒 71 型（EV71）是导致 5 岁以下儿童重症手足口病（HFMD）的主要病原体，目前尚无针对 EV71 的有效药物。因此，迫切需要开发新的药物来控制 EV71 感染。本研究采用 DEAE-纤维素-52 层析法从海带中提取 LJ04，以 0.4 mol/L NaCl 为洗脱液，基于其对微孔板上细胞病变效应评价其抗病毒活性。LJ04 由岩藻糖、半乳糖和甘露糖组成，主要对 EV71 表现出良好的抗病毒活性。LJ04 的抗病毒机制为直接灭活病毒、阻断病毒结合、破坏病毒进入和对非结构蛋白 3C 的弱抑制活性。本研究的两个最重要发现是，LJ04 抑制了人小胶质细胞系 HM1900 细胞中 EV71 的增殖，并且 LJ04 能够在 37°C 下直接在 2 小时内使 EV71 失活。本研究首次证明了海带多糖抑制病毒和 3C 活性的能力；重要的是，对 3C 的抑制可能对 LJ04 的抗病毒作用影响较小。因此，我们的研究结果表明 LJ04 是一种有潜力的候选药物，可用于控制临床严重 EV71 感染。
