Qingfei Paidu decoction (QFPDD) has been clinically proven to be effective in the treatment of
coronavirus disease 2019 (COVID-19). However, the bioactive components and therapeutic mechanisms remain unclear. This study aimed to explore the effective components and underlying mechanisms of QFPDD in the treatment of
COVID-19 by targeting the virus-host interactome and verifying the
antiviral activities of its active components in vitro. Key active components and targets were identified by analysing the topological features of a compound-target-pathway-disease regulatory network of QFPDD for the treatment of
COVID-19. The
antiviral activity of the active components was determined by a live
virus infection assay, and possible mechanisms were analysed by pseudotyped
virus infection and molecular docking assays. The inhibitory effects of the components tested on the virus-induced release of
IL-6, IL-1β and CXCL-10 were detected by ELISA. Three components of QFPDD,
oroxylin A,
hesperetin and
scutellarin, exhibited potent
antiviral activities against live SARS-CoV-2 virus and HCoV-OC43 virus with IC50 values ranging from 18.68 to 63.27 μM.
Oroxylin A inhibited the entry of SARS-CoV-2 pseudovirus into target cells and inhibited
SARS-CoV-2 S protein-mediated cell-cell fusion by binding with the ACE2 receptor. The active components of QFPDD obviously inhibited the
IL-6, IL-1β and CXCL-10 release induced by the
SARS-CoV-2 S protein. This study supports the clinical application of QFPDD and provides an effective analysis method for the in-depth study of the mechanisms of
traditional Chinese medicine (TCM) in the prevention and treatment of
COVID-19.