Analysis of the Active Components and Mechanism of Three Prescriptions in the Treatment of COVID-19 Via Network Pharmacology and Molecular Docking

Abstract

Purpose: Prescriptions of Han-Shi-Yu-Fei (HSYF), Han-Shi-Zu-Fei (HSZF), and Yi-Du-Bi-Fei (YDBF) were effective in treating COVID-19. Based on network pharmacology and molecular docking, overlapping Traditional Chinese medicines (TCMs), their active components, and core targets were explored in this study. Methods: First, the overlapping TCMs and their active components were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) by evaluating Oral Bioactivity (OB) and Drug Likeness (DL). The overlapping targets of potential components and COVID-19 were collected by SwissTargetPrediction, Gene Cards, and Venn 2.1.0 databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were analyzed via DAVID6.8.1 database. Through comprehensive analysis of the “prescriptions-TCMs-components” (P-T-C), “components-targets-pathways” (C-T-P) and “protein–protein interaction” (PPI) networks constructed by Cytoscape 3.7.1 software, the active components and core targets were obtained. Finally, the binding energies of these components with ACE2 and SARS-CoV-2 3CL were analyzed by AutDockTools-1.5.6 and PyMOL software. Results: In all, five overlapping TCMs, 40 potential active components, and 47 candidate targets were obtained and analyzed in these prescriptions. There were 288 GO entries ( P < 0.05), including 211 biological process (BP), 40 cell composition (CC), and 37 molecular function (MF) entries. Most of the 105 KEGG pathways ( P < 0.05) were involved with viral infection and inflammation. Through “PPI” and “C-T-P” networks, the core targets (EGFR, PTGS2, CDK2, GSK3B, PIK3R1, and MAPK3) and active components (Q27134551, acanthoside B, neohesperidin, and irisolidone) with high degrees were obtained. Molecular docking results showed that the above-mentioned four components could inhibit the binding of ACE2 and SARS-COV-2 3CL to protect against COVID-19. Conclusion: In this study, the active components and core targets of three prescriptions in the treatment of COVID-19 were elaborated by network pharmacology and molecular docking, providing a reference for their applications.