Inhibitory effect of Alantolactone against varicella-zoster virus in vitro

Background : Varicella-zoster virus (VZV), a member of the α-herpesvirus family, is known for causing two distinct diseases: chickenpox (varicella) during the primary infection and shingles (zoster) due to reactivation of the virus later in life. Currently, there were vaccines available to prevent VZV infection, but it is not universally effective, and antiviral treatments for VZV are limited and may come with significant side effects. Thus, development of novel therapeutics is urgently needed. Methods: In the current study, we identified a naturally occurring ALT that inhibits replication of recombinant VZV in human diploid fibroblast (WI-38 cells) and Adult Retinal Pigment Epithelial cell line-19 (ARPE-19 cells) through Western blotting, qPCR and plaque assays. The time-of-addition experiment was carried out to identify the stage at which ALT acted. Meanwhile, the transcriptome was applied for the initial exploration of the mechanism underlying anti-VZV activity. Results : We established a screening model for anti-VZV compounds from which we screened ALT with good antiviral efficacy. Our findings revealed that ALT alleviated cytopathic changes, reduced viral titres, and inhibited the expression of viral genes and proteins in WI-38 cells and ARPE-19 cells. Furthermore, our data showed that ALT inhibits VZV infection at both early and late stages of the viral life cycle. Finally, according to RNA-seq data, multiple inflammatory pathways were involved in this antiviral process, and IL-6 was one of the most critical hub genes. Conclusion : Together, our findings identify ALT as a anti-VZV agent that may prove useful in the treatment of VZV replication. Samples include WI-38 cells grouped as Mock (uninfected), DMSO+VZV (solvent control with infection), and ALT+VZV (treatment with infection), harvested at 3dpi. 3 replicates exist for each group.