The potential mechanisms and material basis of Fuzheng Jiedu decoction broad-spectrum inhibiting coronaviruses

Ke Liu; Bixia Hong; Shi-Ting He; Siying Du; Jiayi Ke; Lili Tian; Tao Tao; Yihan Zhang; Kelin Li; Han Chang; Mengzhe Li; Xiaoping An; Lihua Song; Zhongde Zhang; Liang Liu; Hudan Pan; Huahao Fan; Yigang Tong

doi:10.1016/j.virs.2024.12.007

The potential mechanisms and material basis of Fuzheng Jiedu decoction broad-spectrum inhibiting coronaviruses

Virol Sin. 2024 Dec 28:S1995-820X(24)00208-6. doi: 10.1016/j.virs.2024.12.007. Online ahead of print.

Authors

Ke Liu¹, Bixia Hong², Shi-Ting He¹, Siying Du¹, Jiayi Ke¹, Lili Tian¹, Tao Tao¹, Yihan Zhang¹, Kelin Li¹, Han Chang¹, Mengzhe Li¹, Xiaoping An¹, Lihua Song¹, Zhongde Zhang³, Liang Liu³, Hudan Pan⁴, Huahao Fan⁵, Yigang Tong⁶

Affiliations

¹ College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
² School of Basic Medical Science, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511436, China.
³ State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong 510006, China.
⁴ State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong 510006, China. Electronic address: hdpan@gzucm.edu.cn.
⁵ College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China; School of Life Sciences, Tianjin University, Tianjin 300072, China. Electronic address: fanhuahao@tju.edu.cn.
⁶ College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: tongyigang@mail.buct.edu.cn.

PMID: 39736321
DOI: 10.1016/j.virs.2024.12.007

Abstract

Traditional Chinese medicine has unique advantages in preventing and treating COVID-19, and Fuzheng Jiedu decoction (FZJDD) was reported to be effective against COVID-19 in clinical trials. To investigate the potential mechanisms and material basis of FZJDD against SARS-CoV-2, we performed SARS-CoV-2 target protein inhibition analyses and a metabolite full spectrum analysis of FZJDD. Interestingly, FZJDD was found to block the binding of SARS-CoV-2 Spike protein with the receptor ACE2 and inhibit the activity of SARS-CoV-2 3CLpro. Moreover, FZJDD can regulate the TNF and the MAPK signaling pathway to inhibit the inflammatory response and alleviate the "cytokine storm". A total of 298 compounds were identified in FZJDD, among them, caffeic acid and octyl gallate were found to be the potential therapeutic agents of FZJDD. Importantly, FZJDD can broadly inhibit coronavirus infection, including SADS-CoV and porcine epidemic diarrhea virus (PEDV) live viruses, SARS-CoV, MERS-CoV, and SARS-CoV-2 mutant pseudotyped viruses, which might be ascribed to the broad-spectrum anti-coronavirus activity of caffeic acid and octyl gallate. In conclusion, this study reveals the mechanisms and material basis of FZJDD against SARS-CoV-2 and identifies the broad-spectrum anti-coronavirus activity of FZJDD for the first time. Our data provide empirical evidence for the development and application of FZJDD.

Keywords: Fuzheng Jiedu decoction; SARS-CoV-2; broad-spectrum anti- coronavirus; caffeic acid; octyl gallate; traditional Chinese medicine.