大麻二酚和表没食子儿茶素没食子酸酯对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）入侵的多级抑制作用

Multi-level inhibition of SARS-CoV-2 invasion by cannabidiol and epigallocatechin gallate.

作者信息

Zhang Meng-Chun, Wu Hao, Wang Jiaxing, Lu Meixi, Cao Danli, Lin Jingwen, Chen Hang, Lin Caiji, Wang Yao, Zhang Xing-Hua, Xu Mengzhi, Liu Gui-Rong, Li Han, Wang Pengfei, Wang Xiaoyu, Xu Xiaohui, Liu Shu-Lin, Liu Huidi

机构信息

Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, 150081, China; HMU-UCCSM Centre for Infection and Genomics, Harbin Medical University, Harbin, 150081, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China.

Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, 150081, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China; Key Laboratory of Tumor Biotherapy of Heilongjiang Province, Harbin Medical University Cancer Hospital, Harbin, China.

出版信息

Virology. 2025 Sep;610:110579. doi: 10.1016/j.virol.2025.110579. Epub 2025 May 22.

DOI:10.1016/j.virol.2025.110579

PMID:40460494

Abstract

The global pandemic coronavirus disease 2019 (COVID-19) attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study aimed at combination therapies with natural polyphenolic compounds, such as cannabidiol (CBD), green tea polyphenols (Tea-poly), epigallocatechin gallate (EGCG) and theaflavin (TF), to investigate in vitro their inhibitory effects on virus invasion and viral spike (S) protein expression. Among the compounds tested, CBD and Tea-poly exhibited the most significant inhibitory effects on virus entry, comparable to the positive control chloroquine (CQ). EGCG showed the strongest suppression of the expression of the S protein, while CBD remarkably decreased ACE2 expression. CoIP-MS revealed eleven S-protein-interacting proteins that were significantly affected by EGCG. Transcriptome analysis demonstrated similar trends of CBD and EGCG in the modulation of many SARS-CoV-2-associated genes, with CBD showing greater impact on the gene profile than EGCG. GO and KEGG functional enrichment analyses revealed overlapping pathways of EGCG and CBD, including DNA repair, cell-cycle, and ER-, spliceosome- and ribosome-related processes. The combined use of CBD and EGCG can complement each other's advantages in inhibiting the invasion and reinvasion process of the virus at multiple levels, while minimizing the adverse effects of ACE2 expression level changes. Findings in this work offer new information for developing multi-level therapeutic strategies to control SARS-CoV-2 infection and, specifically, provide a novel antiviral agent combination of CBD and EGCG for the control of COVID-19.

摘要

2019年冠状病毒病（COVID-19）全球大流行归因于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。本研究旨在探讨天然多酚化合物联合疗法，如大麻二酚（CBD）、绿茶多酚（Tea-poly）、表没食子儿茶素没食子酸酯（EGCG）和茶黄素（TF），体外研究它们对病毒入侵和病毒刺突（S）蛋白表达的抑制作用。在所测试的化合物中，CBD和Tea-poly对病毒进入表现出最显著的抑制作用，与阳性对照氯喹（CQ）相当。EGCG对S蛋白的表达表现出最强的抑制作用，而CBD显著降低ACE2表达。免疫共沉淀-质谱分析揭示了11种受EGCG显著影响的S蛋白相互作用蛋白。转录组分析表明，CBD和EGCG在调节许多SARS-CoV-2相关基因方面具有相似趋势，其中CBD对基因谱的影响大于EGCG。基因本体（GO）和京都基因与基因组百科全书（KEGG）功能富集分析揭示了EGCG和CBD的重叠途径，包括DNA修复、细胞周期以及与内质网、剪接体和核糖体相关的过程。CBD和EGCG联合使用可以在多个层面上互补各自在抑制病毒入侵和再入侵过程中的优势，同时将ACE2表达水平变化的不利影响降至最低。本研究结果为制定控制SARS-CoV-2感染的多层次治疗策略提供了新信息，特别是为控制COVID-19提供了一种新型的CBD和EGCG抗病毒药物组合。