Drug Screening Based on Network Pharmacology and Molecular Docking Targeting the Brg1/iNOS/HO-1 Signalling Pathway

Abstract

Objective: To investigate the role of Brg1, iNOS, and HO-1 in HSE through network pharmacology, and then targeted the pathway for screening of drugs.

Methods: Firstly, the disease targets of "Herpes Simplex Virus Encephalitis" were collected through TTD, OMIM, Drugbank, Genecards and PharmGKB, and the core targets of Brg1, iNOS, and HO-1 were collected through String database. The core targets of Brg1, iNOS, and HO-1 were collected from String database, and Venn diagrams were created to obtain the intersection of the targets. Then, the literature was reviewed to explore the expression of intersecting targets in diseases and the reverse drug screening was performed by Connectivity Map. After uploading the two intersections to the David database, GO bioenrichment analysis was performed. Finally, the screened drugs were molecularly docked with Brg1, iNOS, and HO-1 to explore the interactions.

Results: Using "Herpes Simplex Virus Encephalitis" as the keyword, 1004 disease targets were screened, and 33 core targets of Brg1, iNOS, and HO-1 and 21 intersecting targets were obtained from the String database. Dipyridamole as a potential drug for the treatment of HSE obtained by reverse drug screening with Connectivity Map. The results of GO suggest that positive regulation of pri-miRNA transcription from RNA polymerase II promoter, response to xenobiotic stimulus, response to drug. Molecular docking showed that dipyridamole binds strongly to Brg1, iNOS, and HO-1.

Conclusion: Dipyridamole can play a role in alleviating HSE by regulating Brg1, iNOS, and HO-1 pathways. This study provides a new idea for the mechanism of HSE occurrence, a new drug for the treatment of HSE, and broadens the clinical application of dipyridamole.