Resveratrol: a potential medication for the prevention and treatment of varicella zoster virus-induced ischemic stroke

Abstract

Background: Infection rate of varicella zoster virus (VZV) is 95% in humans, and VZV infection is strongly associated with ischemic stroke (IS). However, the underlying molecular mechanisms of VZV-induced IS are still unclear, and there are no effective agents to treat and prevent VZV-induced IS.

Objective: By integrating bioinformatics, this study explored the interactions between VZV and IS and potential medication to treat and prevent VZV-induced IS.

Methods: In this study, the VZV and IS datasets from the GEO database were used to specify the common genes. Then, bioinformatics analysis including Gene Ontology, Kyoto Encyclopedia Genes Genomes and Protein-Protein Interaction network analysis was performed. Further, the hub genes, transcription factor (TF) gene interactions, TF-miRNA co-regulatory network and potential drug were obtained. Finally, validation was performed using molecular docking and molecular dynamics simulations.

Results: The potential molecular mechanisms of VZV-induced IS were studied using multiple bioinformatics tools. Ten hub genes were COL1A2, DCN, PDGFRB, ACTA2, etc. TF genes and miRNAs included JUN, FOS, CREB, BRCA1, PPARG, STAT3, miR-29, etc. A series of mechanism may be involved, such as inflammation, oxidative stress, blood-brain barrier disruption, foam cell generation and among others. Finally, we proposed resveratrol as a potential therapeutic medicine for the prevention and treatment of VZV-induced IS. Molecular docking and molecular dynamics results showed that resveratrol and hub genes exhibited strong binding score.

Conclusions: Resveratrol could be an alternative for the prevention and treatment of VZV-IS. More in vivo and in vitro studies are needed in the future to fully explore the molecular mechanisms between VZV and IS and for medication development.

Keywords: Atherosclerosis; Blood–brain barrier; Ischemic stroke; Resveratrol; Varicella zoster virus.

Fig. 1

The workflow of this study. VZV and IS samples were obtained from GSE175797, GSE173719, GSE16561, and GSE22255. Common DEGs were identified from four datasets using the R language. GO identification, KEGG pathway, PPI network, hub genes, TF and miRNA analysis, and medication screening was performed based on the common DEGs. Finally, molecular docking and molecular dynamics simulations were used to validate the resveratrol and hub genes

Fig. 2

Intersection targets of VZV and IS

Fig. 3

GO enrichment analysis of VZV and IS

Fig. 4

Top 10 enrichments of KEGG analysis with VZV and IS

Fig. 5

The PPI network diagram of VZV-IS targets. The nodes closer to the center and the darker color represent that they may play more important role in the whole network. The higher the degree value, the larger the area of the node, and the redder the color, the closer to the center

Fig. 6

The network diagram of 10 hub genes

Fig. 7

The network diagram of hub and TF genes

Fig. 8

The network diagram of hub, TF genes and miRNAs

Fig. 9

Molecular docking diagram of VZV-IS targets and resveratrol

Fig. 10

Profiles of molecular dynamics simulations between target proteins and resveratrol. a RMSD of resveratrol–ACTA2 complex, RMSD of resveratrol–DCN complex and RMSD of resveratrol–ITGA1 complex. b RMSD of resveratrol–PDGFRB complex, RMSD of resveratrol–PRDX1 complex, and RMSD of resveratrol–SPARC complex. c RMSF of resveratrol–ACTA2 complex, RMSF of resveratrol–DCN complex, and RMSF of resveratrol–ITGA1 complex. d RMSF of resveratrol–PDGFRB complex, RMSF of resveratrol–PRDX1 complex, and RMSF of resveratrol–PRDX1 complex