Study on the Potential Material Basis and Molecular Mechanism of Liushen Capsule on the Treatment of COVID-19 Through the Network Pharmacology and Molecular Docking

OBJECTIVE To explore the potential material basis and molecular mechanism of Liushen Capsule on inhibiting COVID-19 through network pharmacology and molecular docking technology. METHODS The effective monomers and targets of realgar， calculus bovis artifacts， borneolum， bufonis venenum and moschus in Liushen Capsule were searched with the help of the network pharmacology databases. Based on UniProt database and Cytoscape 3.6.1 software， the gene corresponding to the target was queried， and the network of traditional Chinese medicine-effective ingredients-effective target was constructed. GO， KEGG， Reactome enrichment analysis were carried out by Metascape platform to predict the mechanism of action. Molecular docking of the top 15 monomers was carried out in the medicinal material-compound-target network with SARS-CoV-2 3CL hydrolase， angiotensin-converting enzyme Ⅱ (ACE2)， and SARS-CoV-2 RNA dependent RNA polymerase (RdRp). RESULTS The network of TCM-active ingredients-effective targets included 5 herbs， 136 compounds and 2 082 targets. The key targets were PTGS2、ESR1、PLA2G1B and PTGS1. The function enrichment analysis of GO was 495 (P<0.05)， of which there were 287 biological processes (BP)， and 96 related items of cell composition (CC)， and 112 molecular function (MF) items. There were 107 signal pathways (P<0.05) in the KEGG pathway enrichment screening， which mainly involved cancer pathway， neuroactive ligand receptor interaction， cell growth， metabolism， apoptosis related pathway， immunity and inflammation. There were 85 signal pathways (P<0.05) in the Reactome pathway enrichment screening， which were mainly involved in nervous system， G protein coupling， interleukin signal， receptor tyrosine kinase signal and gene transcription. The results of molecular docking showed that the affinity of ergotamine， ursolic acid， chenodeoxycholic acid and other core active compounds in Liushen Capsule with SARS-CoV-2 3CL and ACE2 was similar to that of clinically recommended chemicals. CONCLUSION The active compounds in Liushen Capsule， ergotamine， ursolic acid and chenodeoxycholic acid， may regulate multiple signal pathways by binding to ACE2 to act on targets such as PTGS2， ESR1， PLA2G1B and PTGS1， thereby inhibit SARS-CoV-2.