IMB-0523 Inhibits Enterovirus 71 Replication by Activating Signal Transducer and Activator of Transcription 3 Signaling to Upregulate Interferon-Stimulated Genes Expression

Background Hand,foot,and mouth disease caused by enterovirus 71(EV71)infection is prevalent in the Asia-Pacific region in recent years.Currently,no drug is available for the prevention and treatment of EV71 infection.IMB-0523,a N-phenylbenzamide derivative,inhibits hepatitis B virus replication by upregulating the expression of APOBEC3G.In the present study,the effect of IMB-0523 on EV71 replication and related mechanism were investigated.Methods The cytotoxicity of IMB-0523 was determined by cell counting kit.Quantitative real-time polymerase chain reaction and Western blot assay were used to detect the effect of IMB-0523 on EV71 replication and related mechanism.Cytopathic effect assay was used to investigate the effect of IMB-0523 on different EV71 strains,coxsackievirus A16,and coxsackieviruses of group B.Results The results showed that IMB-0523 could dose-dependently inhibit EV71 replication.Preliminary mechanism studies showed that IMB-0523 could activate STAT3 signaling to upregulate the expression of interferon-stimulated genes to play an antiviral role.In addition,IMB-0523 inhibited the replication of different EV71 strains,coxsackievirus A16,and coxsackieviruses of group B.Conclusions IMB-0523 inhibits EV71 replication by activating the STAT3 signaling pathway to upregulate interferon-stimulated gene expression.IMB-0523 has broad-spectrum antiviral potential and may be used as a lead compound for the development of broad spectrum antiviral drugs.