A Network Pharmacology Study to Uncover the Multiple Molecular Mechanism of the Chinese Patent Medicine Toujiequwen Granules in the Treatment of Corona Virus Disease 2019 (COVID-19)

Yang, Bao-yu; Wang, Hao-zhen; Ma, Zhen-zhong; Lu, Chen; Li, Yang; Lu, Zi-yin; Lu, Xiu-li; Gao, Bing

Since the outbreak of the novel corona virus disease 2019 (COVID-19) at the end of 2019, specific antiviral drugs have been lacking. A Chinese patent medicine 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 Toujiequwen granules. Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin. Drug targets most affected by the active ingredients were PTGS2, PTGS1, and DPP4. Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases. An “active ingredient-target-disease” network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19. There were 53 ingredients that could act on DPP4, suggesting that DPP4 may become a potential new key target for the treatment of COVID-19. 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 and endocrine resistance pathway. The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against multiple signaling pathways related to the pathogenesis of COVID-19.