Department of Cell Biology, School of Life Sciences, Central South University, Changsha 410013, China; Department of Infectious Diseases, Guizhou Provincial People's Hospital, Guizhou 550000, China.
Department of Cell Biology, School of Life Sciences, Central South University, Changsha 410013, China.
Int J Biol Macromol. 2021 Apr 15;176:1-12. doi: 10.1016/j.ijbiomac.2021.02.012. Epub 2021 Feb 4.
SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 μM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 μM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19.
SARS-CoV-2 是导致 2019 年冠状病毒病（COVID-19）大流行的病原体。SARS-CoV-2 的主要蛋白酶 3CLpro，由于其在病毒复制和病毒蛋白基因表达中的不可或缺作用，是抗病毒抑制剂的一个有吸引力的靶标。目前广泛研究寻找能够有效抑制 3CLpro 关键活性的化合物，从而干扰病毒生命周期。在这里，我们报告表没食子儿茶素-3-没食子酸酯（EGCG），一种中草药（CHM）的活性成分，是一种有效的 3CLpro 抑制剂，其半最大抑制浓度（IC50）为 0.874±0.005μM。在研究中，我们回顾性分析了 123 例 COVID-19 患者的临床数据，发现了三个有效的中药方剂。我们采用多种策略从中药的活性成分中筛选出有效的 SARS-CoV-2 3CLpro 抑制剂，包括网络药理学、分子对接、表面等离子体共振（SPR）结合测定和荧光共振能量转移（FRET）抑制测定。SPR 测定显示 EGCG 与 3CLpro 之间具有良好的相互作用，KD~6.17μM，表明 EGCG 与 SARS-CoV-2 3CLpro 具有较高的亲和力。我们的研究结果为 EGCG 作为 COVID-19 潜在治疗药物的作用机制提供了重要的见解。
