Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus (CV) and respiratory syncytial virus (RSV). However, no antiviral agents with low toxicity and drug resistance are currently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin (an ingredient of Rheum palmatum) against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum palmatum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication inhibition, virucidal and anti-absorption effects, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tet-razolium bromide (MTT) assay and plaque reduction assay (PRA). The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR (qPCR). Cytokine (IFN-γ, TNF-α) mRNA expressions after emodin treatment (7.5, 15, 30 μmol/L) were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration (EC50) ranging from 13.06 to 14.27 μmol/L and selectivity index (SI) being 5.38-6.41 μmol/L. However, emodin couldn't directly inactivate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.

中文翻译：

---

大黄大黄素的大黄素在体外对弓形病毒B5和人呼吸道合胞病毒的抗病毒作用。

病毒感染是全世界老年人和幼儿发病和死亡的主要原因。最常见的病原体包括柯萨奇病毒（CV）和呼吸道合胞病毒（RSV）。但是，目前在临床治疗中没有低毒性和耐药性的抗病毒药。本研究旨在检查大黄素（大黄的成分）对CVB5和RSV感染的抗病毒活性，以试图发现用于病毒感染的新抗病毒药物。提取大黄素单体并从大黄提取。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基-2H-tet-评估了大黄素对HEp-2细胞的抗病毒活性，包括病毒复制抑制，杀病毒和抗吸收作用。溴化咪唑（MTT）测定和噬菌斑减少测定（PRA）。通过噬菌斑测定和定量实时PCR（qPCR）进一步测定大黄素在14 h内抑制病毒的动力学。大黄素处理后（7.5、15、30μmol/ L）也通过感染后qPCR评估了细胞因子（IFN-γ，TNF-α）的mRNA表达。结果表明，大黄素具有有效的抑制CVB5和RSV的活性，其50％有效浓度（EC50）为13.06至14.27μmol/ L，选择性指数（SI）为5.38-6.41μmol/ L。但是，大黄素不能直接灭活病毒或阻止其吸收到细胞中。它以浓度和时间依赖性方式，特别是在感染后的最初0-4小时内，作为针对CVB4和RSV的生物合成抑制剂。而且，大黄素与体外病毒对照组相比，可降低IFN-α的mRNA表达，但可显着增强TNF-γ的表达。我们的结果为大黄素在临床治疗中开发为人类肠道病毒和呼吸道病毒感染的新型安全抗病毒剂提供了分子基础。