ABSTRACT
Objective: To explore the action mechanism of five Chinese medicines targeting ACE2 for the treatment of COVID-19. Methods: Chinese medicines with human angiotensin converting enzyme II (ACE2) targeting activity were screened through the traditional Chinese medicine (TCM) system pharmacology database and analysis platform (TCMSP), and the TCMSP platform was further utilized to identify the active ingredients of Chinese medicines and their corresponding drug targets. Then, the protein interaction of the above protein targets was analyzed by STRING online database and the relevant data were downloaded. Next, the core sub-network modules in the PPI network system were screened through the MCODE plug-in in CytoScape 3.2.1 software. The functional enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) were carried out, using online enrichment analysis software DAVID v6.8, to predict the pharmacological mechanism of the above five Chinese medicines, and to verify and explore the feasibility of compatibility and clinical application of related herb-pair or formula under the theoretical system of TCM. Results: Five Chinese medicines with potential therapeutic effects on ACE2 were selected through the TCMSP platform, namely Bupleuri Radix, Puerariae Lobatae Radix, Puerariae Lobatae Flos, Cyathulae Radix, and Hemerocallis Radix, which contained 42 active ingredients and 240 drug targets. The results of GO biological function enrichment analysis showed that the above five Chinese medicines could affect the biological processes such as inflammatory response, cell apoptosis and proliferation and etc. The results of KEGG pathway enrichment analysis showed that the pharmacological mechanisms of these Chinese medicines were closely related to PI3K-Akt pathway, TNF pathway, FoxO pathway, MAPK pathway, and so on. In TCM theory, Bupleuri Radix and Puerariae Lobatae Radix is a classic herb-pair for the treatment of infectious and febrile diseases. Chaige Jieji Decoction is widely used in febrile diseases in ancient and modern clinics, and has achieved good clinical effects. The main febrile disease treated by this herb-pair is the triple-yang combination of diseases in the syndrome differentiation of the six meridians, which is in line with the syndrome differentiation of TCM in patients with SARS-CoV-2 infection. It can be used with Cyathulae Radix and Hemerocallis Radix in addition and subtraction. Conclusion: The identified five Chinese medicines have multi-target, multi-function and multi-pathway pharmacological effects on the treatment of COVID-19. According to the theoretical analysis of TCM and previous clinical experience, it is suggested that Chaige Jieji Decoction or Bupleuri Radix and Puerariae Lobatae Radix herb-pair can be used to treat COVID-19.