Bee-derived propolis shows potent antiviral activity against varicella-zoster virus

Announcing a new article publication for Zoonoses journal. Varicella-zoster virus (VZV) is a clinically important human neurotropic herpesvirus that causes varicella (chickenpox) as primary infection, typically in children. After primary infection, VZV establishes lifelong latency in sensory ganglia and can later reactivate and cause herpes zoster (shingles).

Globally, varicella and shingles affect a substantial number of individuals each year. Although people with shingles can recover without specific antiviral treatment, the persistent, often severe pain associated with the disease can lead to depression and significantly decrease quality of life. Currently, acyclovir and its derivatives or similar compounds are the primary FDA-approved treatments for VZV infection. However, resistance to acyclovir, often because of mutations in the viral thymidine kinase, is increasingly observed in clinical settings. Therefore, alternative antiviral strategies against VZV are needed. Propolis (also known as "bee glue"), a resin-like substance produced by bees, has well-documented antibacterial and anti-inflammatory properties. The authors of this article investigated the antiviral potential of propolis against VZV in in vitro systems including a cell culture model, human skin, and human dorsal root ganglia (DRG) tissue.

ARPE-19 cells, human fetal skin, DRG tissues, and the VZV pOka-Luc-GFP strain (expressing luciferase and GFP for viral monitoring) were used. Propolis (Brazilian green propolis in DMSO) cytotoxicity was assessed with MTT assays. Viral replication was quantified with time-dependent luciferase assays. RNA sequencing (RNA-seq) was performed to analyze differential gene expression in propolis-treated (0.0625% and 0.125%) and control cells (with/without VZV), and was followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Additionally, an acyclovir-resistant VZV mutant (VZV-delTK, lacking the thymidine kinase gene ORF36) was generated with BAC technology for a mechanistic comparison of propolis and acyclovir.

MTT assays indicated that propolis at ≤0.125% had low cytotoxicity to ARPE-19 cells. Luciferase assays demonstrated that propolis inhibited VZV replication in a concentration-dependent manner. This efficacy was consistent in skin and DRG tissues, in which 0.1% propolis approached acyclovir's antiviral activity. RNA-seq revealed that propolis altered host gene expression. Among the 207-1035 differentially expressed genes identified across concentrations, the enriched pathways included glycolysis/gluconeogenesis, calcium signaling, and ferroptosis. Propolis also inhibited VZV RNA transcription and splicing. Notably, propolis effectively inhibited the acyclovir-resistant strain VZV-delTK, whereas acyclovir did not, thus confirming the treatments' distinct mechanisms.

Propolis exhibited significant antiviral activity against VZV in both cellular and tissue models, through a mechanism distinct from that of acyclovir. These results support further investigation of propolis as a potential anti-VZV agent with a novel mechanism of action.