Utilizing network pharmacology to explore the underlying mechanism of Cinnamomi Ramulus in Zika Fever induced by Zika Virus

Abstract

Background: Zika fever is a mosquito-borne infection induced by Zika virus (ZIKV),effective drug and vaccine against ZIKV infection is still unavailable. Cinnamomi ramulus (CR) is a traditional Chinese herb with a long history ,can stimulate secretion of sweat and relieve exterior syndrome. The aim of this research was to evaluate the effect of CR against ZIKV and uncover its mechanism of action by network pharmacology.Methods: Cell viability assay, qRT-PCR assay and western blot assays were perfermed to evaluate anti-ZIKV activity in vitro. Survival rate, body weight were observed and viremia was detected in AG6 mice. Drug- target-disease networks, GO enrichment, and KEGG pathway analysis was established to clarify the therapeutic mechanismsits. Results: In this study, we find that CR can alleviate CPE after Zika virus infection. In the premixed administration mode, CR showed superior activity to inhibit viral RNA replication and protein expression in cells. Orally administered CR effectively protected AG6 mice infected with lethal doses of ZIKV, conferring 50% or 20% survival rate at a dosage of 900mg/ml or 450mg/ml, reducing body weight loss, inhibiting viral RNA replication. Beta-sitosterol, DBP, α-Longipinen, (-)-alpha-cedrene, ()-alpha-Longipinene may the main active compound and PTGS2, GABRA1, PTGS1, PTGES and CCR5 may the main targets. 176 biological processes, 16 cell components, 27 molecular functions, and 37 pathways were significantly identified in GO enrichment and pathway analysis. Conclusions: These results reveal that CR treatment of Zika fever is mainly related to PTGS1 and PTGS2 regulated prostaglandin release, metabolism, and inflammation response.