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

• Published in: Cell & bioscience 2023-06, Vol.13 (1), p.118-118, Article 118
• Main Authors: Cheng, Fang-Ju, Ho, Chien-Yi, Li, Tzong-Shiun, Chen, Yeh, Yeh, Yi-Lun, Wei, Ya-Ling, Huynh, Thanh Kieu, Chen, Bo-Rong, Ko, Hung-Yu, Hsueh, Chen-Si, Tan, Ming, Wu, Yang-Chang, Huang, Hui-Chi, Tang, Chih-Hsin, Chen, Chia-Hung, Tu, Chih-Yen, Huang, Wei-Chien
• Format: Article
• Language: English
• Subjects: ACE2; Allergic reaction; Allergy; Angiotensin; Angiotensin-converting enzyme 2; Antihistamines; Artemisia argyi; China; Chinese medicine; Coronaviruses; Coumarins; COVID-19; Cytotoxicity; Disease transmission; Epidemics; Eriodictyol; Health aspects; Infections; Inflammation; Lymphocytes T; Oral administration; Pandemics; Peptidyl-dipeptidase A; Phytochemicals; Prevention; Proteases; Protein binding; Proteins; Respiratory diseases; SARS-CoV-2 variants; Serine proteinase; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; T cells; TMPRSS2; Umbelliferone; Viruses
• ISSN: 2045-3701; 2045-3701
• DOI: 10.1186/s13578-023-01070-y

Artemisia 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. Among 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. Eriodictyol 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.