汉防己甲素（KD-1）通过抑制核因子 kappa B（NF-κB）信号通路，对新型冠状病毒（SARS-CoV-2）和人类冠状病毒 229E（HCoV-229E）发挥抗病毒和抗炎作用。
Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway.
机构信息
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Kunming University of Science and Technology Library, Kunming, China.
出版信息
Phytomedicine. 2020 Nov;78:153296. doi: 10.1016/j.phymed.2020.153296. Epub 2020 Aug 1.
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has extensively and rapidly spread in the world, causing an outbreak of acute infectious pneumonia. However, no specific antiviral drugs or vaccines can be used. Phillyrin (KD-1), a representative ingredient of Forsythia suspensa, possesses anti-inflammatory, anti-oxidant, and antiviral activities. However, little is known about the antiviral abilities and mechanism of KD-1 against SARS-CoV-2 and human coronavirus 229E (HCoV-229E).
PURPOSE
The study was designed to investigate the antiviral and anti-inflammatory activities of KD-1 against the novel SARS-CoV-2 and HCoV-229E and its potential effect in regulating host immune response in vitro.
METHODS
The antiviral activities of KD-1 against SARS-CoV-2 and HCoV-229E were assessed in Vero E6 cells using cytopathic effect and plaque-reduction assay. Proinflammatory cytokine expression levels upon infection with SARS-CoV-2 and HCoV-229E infection in Huh-7 cells were measured by real-time quantitative PCR assays. Western blot assay was used to determine the protein expression of nuclear factor kappa B (NF-κB) p65, p-NF-κB p65, IκBα, and p-IκBα in Huh-7 cells, which are the key targets of the NF-κB pathway.
RESULTS
KD-1 could significantly inhibit SARS-CoV-2 and HCoV-229E replication in vitro. KD-1 could also markedly reduce the production of proinflammatory cytokines (TNF-α, IL-6, IL-1β, MCP-1, and IP-10) at the mRNA levels. Moreover, KD-1 could significantly reduce the protein expression of p-NF-κB p65, NF-κB p65, and p-IκBα, while increasing the expression of IκBα in Huh-7 cells.
CONCLUSIONS
KD-1 could significantly inhibit virus proliferation in vitro, the up-regulated expression of proinflammatory cytokines induced by SARS-CoV-2 and HCoV-229E by regulating the activity of the NF-кB signaling pathway. Our findings indicated that KD-1 protected against virus attack and can thus be used as a novel strategy for controlling the coronavirus disease 2019.
背景
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在世界范围内广泛而迅速传播，导致急性传染性肺炎爆发。然而，目前尚无特效的抗病毒药物或疫苗可用。连翘酚（KD-1）是连翘的代表性成分，具有抗炎、抗氧化和抗病毒作用。然而，关于 KD-1 对 SARS-CoV-2 和人冠状病毒 229E（HCoV-229E）的抗病毒能力和机制知之甚少。
目的
本研究旨在探讨 KD-1 对新型 SARS-CoV-2 和 HCoV-229E 的抗病毒和抗炎活性及其在体外调节宿主免疫反应的潜在作用。
方法
采用细胞病变效应和蚀斑减少法评估 KD-1 对 SARS-CoV-2 和 HCoV-229E 的抗病毒活性。采用实时定量 PCR 法检测 SARS-CoV-2 和 HCoV-229E 感染后 Huh-7 细胞中促炎细胞因子的表达水平。Western blot 法测定 Huh-7 细胞中核因子 kappa B（NF-κB）p65、p-NF-κB p65、IκBα和 p-IκBα的蛋白表达，这些蛋白是 NF-κB 通路的关键靶点。
结果
KD-1 可显著抑制 SARS-CoV-2 和 HCoV-229E 在体外的复制。KD-1 还可显著降低 TNF-α、IL-6、IL-1β、MCP-1 和 IP-10 等促炎细胞因子在 mRNA 水平上的产生。此外，KD-1 可显著降低 Huh-7 细胞中 p-NF-κB p65、NF-κB p65 和 p-IκBα的蛋白表达，同时增加 IκBα的表达。
结论
KD-1 可显著抑制病毒在体外的增殖，通过调节 NF-кB 信号通路的活性，抑制 SARS-CoV-2 和 HCoV-229E 诱导的促炎细胞因子的上调表达。我们的研究结果表明，KD-1 可抵御病毒攻击，因此可作为控制 2019 年冠状病毒病的新策略。
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