A Network Pharmacology Study to Uncover the Multiple Molecular Mechanism of the Chinese Patent Medicine Toujiequwen Granules in the Treatment of Corona Virus Disease (COVID-19)

Since the outbreak of the novel Corona Virus Disease 2019 (COVID-19) infected by SARS-CoV-2 at the end of 2019, clinical specific antiviral drugs have been lacking. A Chinese patent medicine called ‘Toujiequwen Granules’ has been promoted in the treatment of COVID-19. The present study was designed to reveal the molecular mechanism of Toujiequwen Granules against COVID-19. A network pharmacological method was applied to screen the main active ingredients of Tongjiequwen Granules. Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredients interacting with many drug targets are quercetin., drug targets most affected by the active ingredients are PTGS2, PTGS1, and DPP4. Drug target disease enrichment analysis showed drug targets are significantly enriched in cardiovascular diseases, digestive tract diseases and so forth. An ‘active ingredient-target-disease’ network showed that 57 active ingredients from Toujiequwen Granules, interact with 15 key targets of coronary pneumonia. There are 53 ingredients that can act on DPP4, suggesting that DPP4 may become a potential new key target for the treatment of COVID-19. The GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity and other functions. KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors endocrine resistance pathway, and others. These evidences suggest that Toujiequwen Granules might play an effective role through improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against multiple signaling pathways related to the pathogenesis of SARS-CoV-2.