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. Although there are vaccines available to prevent VZV infection, it is still 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: We identified a naturally occurring Alantolactone (ALT) that inhibited 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. Subsequently, we explored the mechanism underlying the anti-VZV activity of ALT using time-of-addition experiments and transcriptomic analyses. RESULTS: A screening model was established for anti-VZV compounds, and we screened ALT was with good anti-VZV 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 inhibited VZV infection in intracellular viral replication. Finally, multiple inflammatory pathways were involved in the antiviral role of ALT, and IL-6 was one of the most critical hub genes. CONCLUSION: Together, our findings identify ALT as an anti-VZV agent that may prove useful in the treatment of VZV replication.