The anti-SARS-CoV-2 effect and mechanism of Chiehyuan herbal oral protection solution

Ching-Yuan Wu; Yao-Hsu Yang; Yu-Shih Lin; Li-Hsin Shu; Yu-Ching Cheng; Hung-Te Liu; Yin-Yin Lin; I-Yun Lee; Wei-Tai Shih; Pei-Rung Yang; Ying-Ying Tsai; Geng-He Chang; Cheng-Ming Hsu; Reming-Albert Yeh; Yu-Huei Wu; Yu-Heng Wu; Rou-Chen Shen; Ming-Shao Tsai

doi:10.1016/j.heliyon.2023.e17701

The anti-SARS-CoV-2 effect and mechanism of Chiehyuan herbal oral protection solution

Heliyon. 2023 Jul 3;9(7):e17701. doi: 10.1016/j.heliyon.2023.e17701. eCollection 2023 Jul.

Authors

Ching-Yuan Wu^{1

2

3}, Yao-Hsu Yang^{1

2}, Yu-Shih Lin⁴, Li-Hsin Shu¹, Yu-Ching Cheng^{1

5}, Hung-Te Liu¹, Yin-Yin Lin¹, I-Yun Lee¹, Wei-Tai Shih¹, Pei-Rung Yang¹, Ying-Ying Tsai¹, Geng-He Chang^{5

6

7}, Cheng-Ming Hsu^{5

6}, Reming-Albert Yeh⁵, Yu-Huei Wu⁸, Yu-Heng Wu⁹, Rou-Chen Shen⁵, Ming-Shao Tsai^{5

6}

Affiliations

¹ Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
² School of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
⁴ Department of Pharmacy, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
⁵ Department of Otolaryngology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
⁶ Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁷ Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi, Taiwan.
⁸ Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
⁹ Department of Electrical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan.

Abstract

The Chiehyuan herbal oral protection solution (GB-2) is a herbal mixture commonly utilized in Taiwan for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per traditional Chinese medicine practices. This study assessed the clinical impact of GB-2 through prospective clinical trials. With twice-daily use for a week, GB-2 was shown to diminish the expression of angiotensin-converting enzyme 2 (ACE2) in oral mucosal cells. Moreover, after two weeks of use, it could reduce transmembrane protease, serine 2 (TMRPSS2) expression in these cells. Additionally, in vitro experiments demonstrated that GB-2 lessened the entry efficiency of the Omicron, L452R-D614G, T478K-D614G, and L452R-T478K-D614G variants of the SARS-CoV-2 pseudotyped lentivirus. It also impeded the interaction between ACE2 and the receptor-binding domain (RBD) presenting N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R and L452R-T478K mutations. Glycyrrhizic acid, a major compound in GB-2, also hindered the entry of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus by obstructing the binding between ACE2 and the RBD presenting the N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R mutation. To sum up, these findings suggest that GB-2 can decrease ACE2 and TMPRSS2 expression in oral mucosal cells. Both glycyrrhizic acid and GB-2 were found to reduce the entry efficiency of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus and block the binding between ACE2 and the RBD with the N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R mutation. This evidence implies that GB-2 might be a potential candidate for further study as a preventative measure against SARS-CoV-2 infection.

Keywords: ACE2; Mouth washing; Omicron variant; SARS-CoV-2; Spike protein; TMPRSS2.