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

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.