Investigate mechanism of Jinzhen Oral Liquid for prevention COVID-19 based on network pharmacology and molecular docking technology

ABSTRACT

Objective: To investigate the mechanism of Jinzhen Oral Liquid (JOL) for prevention COVID-19 through network pharmacology and molecular docking technology. Methods: The protein targets related to COVID-19 were searched by literature mining and retrieving in DisGeNET, OMIM, KEGG and UniProt databases. With the aid of Traditional Chinese Medicine Network Pharmacology Intelligent Information Platform (TCMN) searching JOL chemical components and targets, the "herb-compound-target network" was constructed using Cytoscape-3.2.1 software to predict the main active ingredients and action targets of JOL in the treatment of COVID-19. The crystal structure of novel coronavirus (SARS-CoV-2) 3CL hydrolase (3CLpro) and angiotensin converting enzyme II (ACE2) was retrieved from the RCSB PDB database, and the active compounds were docked with the two proteins by using AutoDock Vina software. Results: The herb-compound-target network contained 75 compounds including isoglabrolide, peimisine, and sennoside B, etc., which are from the three medicinal materials of Glycyrrhiza uralensis, Rheum officinale, and Fritillaria ussuriensis, and 28 targets including mammalian target of rapamycin (mTOR), Janus kinase 3 (JAK3) and mitogen-activated protein kinase 1 (MEK1). Furthermore, nine key compounds (isoglabrolide, glabrolide, ebeiedinone, desoxo- glabrolid-acetate, peimisine, verticinone, imperialine, ussuriedinone and euchrenone A5) and 10 potential targets (mTOR, JAK3, ACE2, TNFA, AKT2, PIK3CA, MEK1, BRD2, ACE and ANPEP) of JOL were predicted for treating COVID-19 by network characteristic analysis. The molecular docking results showed that some core compounds of JOL had a certain degree of affinity for 3CLpro and ACE2. Conclusion: JOL may inhibit the occurrence and development of cytokine storm in COVID-19 by regulating the expression of Brd2, CD13, and ACE2 and interfering with the PI3K/Akt, Jak-STAT, TNF and MAPK signaling pathways, and inhibit virus replication by binding with 3CLpro, thus exerting a preventive or therapeutic effect on COVID-19.