Background and Purpose:Coronavirus disease 2019 (COVID-19) is a lifethreatening
disease worldwide due to its high infection and serious outcomes resulting from
acute lung injury. Qingwen Baidu decoction (QBD), a well-known herbal prescription, has
shown significant efficacy in patients with Coronavirus disease 2019. Hence, this study aims to
uncover the molecular mechanism of QBD in treating COVID-19-related lung injury.Methods:Traditional Chinese Medicine Systems Pharmacology database (TCMSP), DrugBanks
database, and Chinese Knowledge Infrastructure Project (CNKI) were used to retrieve the active
ingredients of QBD. Drug and disease targets were collected using UniProt and Online Mendelian
Inheritance in Man databases (OMIM). The core targets of QBD for pneumonia were analyzed
by the Protein-Protein Interaction Network (PPI), Gene Ontology (GO), and Kyoto Encyclopedia
of Genes and Genomes (KEGG) to reveal the underlying molecular mechanisms. The
analysis of key targets using molecular docking and animal experiments was also validated.Results:A compound-direct-acting target network mainly containing 171 compounds and 110
corresponding direct targets was constructed. The key targets included STAT3, c-JUN, TNF-α,
MAPK3, MAPK1, FOS, PPARG, MAPK8, IFNG, NFκB1, etc. Moreover, 117 signaling pathways
mainly involved in cytokine storm, inflammatory response, immune stress, oxidative stress
and glucose metabolism were found by KEGG. The molecular docking results showed that the
quercetin, alanine, and kaempferol in QBD demonstrated the strongest affinity to STAT3, c-
JUN, and TNF-α. Experimental results displayed that QBD could effectively reduce the pathological
damage to lung tissue by LPS and significantly alleviate the expression levels of the three
key targets, thus playing a potential therapeutic role in COVID-19.Conclusion:QBD might be a promising therapeutic agent for COVID-19 via ameliorating
STAT3-related signals.