Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology

Table 4 The comparison and advantage of this research work with the recently published paper in the Traditional Medicine Research journal

Study	Compounds of XBJ^a	Targets of XBJ^b	Potential targets of COVID-19	Results	Software and tools	Combine with other targets^c
Zhang et al	Based on TCMSP database (2014 version) with oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18.	TCMSP database.	Based on the GeneCards database.	8 key compounds: Luteolin, Quercetin, Baicalein, Kaempferol, Tanshinone II A, Myricanone, Dan-shexinkum d, Ellagic acid. 15 key targets: DPP4, AR, ESR1, CALM1, AKT1, CASP3, NOS3, VEGF-A, TP53, BCL2, TNF, JUN, CDKN1A, FOS and BAX.	Topology analysis: Network Analyzer. Network construction: Cytoscape. Enrichment analysis: Metascape, DAVID database. Molecular docking: Ligand Docking module of Schrödinger.	NO.
The current research	Selected active ingredients that had been detected by liquid chromatography-mass spectrometry (LC-MS).	Swiss database.	On the basis of Zhang’s research, we added two ways to search for disease targets, including literature search and ACE co-expressed genes.	18 key compounds were showed in Fig. 8. 10 key targets: GAPDH, ALB, TNF, EGFR, MAPK1, CASP3, STAT3, MAPK8, PTGS2, JUN, IL-2, ESR1, and MAPK14.	Topology analysis: STRING and cytoHubba. Network construction: Cytoscape. Enrichment analysis: R software 3.5.2, org.Hs.eg.db package, clusterProfiler package, and ClueGO. Molecular docking: Auto Dock vina, AutoDockTools, Protein Data Bank, and PyMOL.	YES. Combine with other targets like putative COVID-19-interacting human proteins.

^aOB is an index used to screen active ingredients administered orally and is not suitable for intravenous injections, while XBJ is administered intravenously. OB and DL are often used to screen the effective ingredients of Chinese medicine compounds administered by oral route, the injection do not need to be absorbed through the gastrointestinal tract
^bThe latest update time of TCMSP was 2014, it is questionable whether overly lagging knowledge can facilitate mechanistic investigations of TCM against COVID-19. So, we used Swiss database (on-line since 2014, and the latest update time was 2019) to predict the targets of XBJ
^cAll 332 virus-interacting human proteins were obtained from STRING (https://string-db.org/cgi/covid.pl)

ISSN: 1756-0381