Umbelliferone and eriodictyol suppress the cellular entry of SARS-CoV-2

Cell & Bioscience

Research

Thanh Kieu Huynh¹  Yi-Lun Yeh¹  Ya-Ling Wei¹  Wei-Chien Huang²  Bo-Rong Chen³  Fang-Ju Cheng³  Yang-Chang Wu⁴  Hung-Yu Ko⁵  Chien-Yi Ho⁶  Hui-Chi Huang⁷  Yeh Chen⁸  Tzong-Shiun Li⁹  Ming Tan^1,10  Chih-Hsin Tang^1,11  Chia-Hung Chen^1,12  Chih-Yen Tu^1,12  Chen-Si Hsueh^1,13 

[1] Center for Molecular Medicine, China Medical University Hospital, 404, Taichung, Taiwan;Graduate Institute of Biomedical Sciences, China Medical University, 404, Taichung, Taiwan;Center for Molecular Medicine, China Medical University Hospital, 404, Taichung, Taiwan;Graduate Institute of Biomedical Sciences, China Medical University, 404, Taichung, Taiwan;Department of Medical Research, China Medical University Hsinchu Hospital, 302, Hsinchu, Taiwan;Department of Medical Laboratory Science and Biotechnology, Asia University, 413, Taichung, Taiwan;Drug Development Center, China Medical University, 404, Taichung, Taiwan;Center for Molecular Medicine, China Medical University Hospital, 404, Taichung, Taiwan;Graduate Institute of Biomedical Sciences, China Medical University, 404, Taichung, Taiwan;School of Medicine, China Medical University, 404, Taichung, Taiwan;Chinese Medicine Research and Development Center, China Medical University Hospital, 404, Taichung, Taiwan;Graduate Institute of Integrated Medicine, China Medical University, 404, Taichung, Taiwan;Department of Medical Laboratory Science and Biotechnology, Asia University, 413, Taichung, Taiwan;Cognitive Science, University of California San Diego, 92093, San Diego, CA, USA;Department of Biomedical Imaging and Radiological Science, China Medical University, 404, Taichung, Taiwan;Division of Family Medicine, Physical Examination Center, China Medical University Hsinchu Hospital, 302, Hsinchu, Taiwan;Department of Medical Research, China Medical University Hsinchu Hospital, 302, Hsinchu, Taiwan;Department of Chinese Pharmaceutical Science and Chinese Medicine Resources, China Medical University, 404, Taichung, Taiwan;Department of Food Science and Biotechnology, National Chung Hsing University, 402, Taichung, Taiwan;Department of Plastic Surgery, and Innovation Research Center, Show Chwan Memorial Hospital, 500, Changhua, Taiwan;Graduate Institute of Biomedical Engineering, National Chung Hsing University, 402, Taichung, Taiwan;Graduate Institute of Biomedical Sciences, China Medical University, 404, Taichung, Taiwan;School of Medicine, China Medical University, 404, Taichung, Taiwan;School of Medicine, China Medical University, 404, Taichung, Taiwan;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 404, Taichung, Taiwan;Department of Respiratory Therapy, China Medical University, 404, Taichung, Taiwan;Taichung Girls’ Senior High School, 403, Taichung, Taiwan;

关键词: Artemisia argyi;    Eriodictyol;    Umbelliferone;    TMPRSS2;    ACE2;    SARS-CoV-2 variants;   

DOI  :  10.1186/s13578-023-01070-y

 received in 2022-12-11, accepted in 2023-06-13,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundArtemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study.ResultsAmong the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice.ConclusionsEriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

40517_2023_259_Article_IEq86.gif

40517_2023_259_Article_IEq89.gif

40517_2023_259_Article_IEq31.gif

40517_2023_259_Article_IEq16.gif

Fig. 2

40517_2023_259_Article_IEq7.gif

40517_2023_259_Article_IEq6.gif

40517_2023_259_Article_IEq5.gif

13011_2023_540_Article_IEq19.gif

Fig. 2

40517_2023_259_Article_IEq1.gif

13011_2023_540_Article_IEq14.gif

Fig. 1

13011_2023_540_Article_IEq10.gif

Fig. 7

13011_2023_540_Article_IEq7.gif

13011_2023_540_Article_IEq6.gif

Fig. 1

41116_2023_37_Article_IEq275.gif

41116_2023_37_Article_IEq252.gif

41116_2023_37_Article_IEq245.gif

41116_2023_37_Article_IEq188.gif

Fig. 6

41116_2023_37_Article_IEq72.gif