Network pharmacological analysis and mechanism prediction of Xingnaojing Injection in treatment of neurological damage caused by SARS-CoV-2 / 中草药

ABSTRACT

Objective: To explore the active compounds, targets and signaling pathways of Xingnaojing Injection (XNJI) for the treatment of neurological damage caused by SARS-CoV-2, so as to explore its mechanism. Methods: Using TCMSP, BATMAN, Swiss Target Prediction, and other databases, the chemical compounds and targets of XNJI were retrieved. Cytoscape software was used to construct XNJI efficacy network of "drug-compounds-targets" for coronavirus and neuroprotection, and the action mechanism was predicted by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then core compounds were verified by molecular docking with 3CL Mpro, ACE2, and 2019-nCoV RBD/ACE2-B0AT1 complex. Results: A total of 105 active compounds of XNJI, 928 drug targets, 741 targets of coronavirus, 611 targets of neuroprotection, 83 drug-disease common targets, 12 core compounds, and seven key targets were obtained. The function enrichment analysis of GO yielded 204 entries, KEGG pathway enrichment screened 120 signaling pathways, which included Hepatitis B, pathways in cancer, TNF, HIF-1, and VEGF signaling pathway, and so on. The results of molecular docking showed that core compounds of XNJI had a good bonding activity with 3CL Mpro, ACE2 and complex. The chlorogenin and kaempferol had the lowest binding energy with three proteins and might play an important role in treatment. Conclusion: The core compounds in XNJI including chlorogenin, kaempferol, 5-hydroxy- 6,7,3',4',5'-pentamethoxyflavone, 3-methylkempferol, morin, gardenin, quercetin, artemisetin, genistein, dryobalanone, curcumin, and elemicin, which might interfere with various signaling pathways by acting on key targets like PARP1, PTGS2, MMP9, CDK2, ADORA2A, ALOX5, GSK3B, and regulate the inflammatory response, apoptosis, oxidative stress, angiogenesis, and other processes to improve the neurological damage caused by SARS-CoV-2, and inhibit virus replication and prevent infection of the host cell by binding with 3CL Mpro, ACE2 and complex, which suggest that XNJI may have a positive therapeutic effect on the neurological damage caused by SARS-CoV-2.