Abstract
Archangiumide is a unique macrolide natural product that features an endocyclic allene functionality, rendering it a prototype of a new class of secondary metabolites of microbial origin. However, its biological and/or pharmaceutical roles remain obscure. In this study, we have unveiled an antiviral potency of archangiumide that was effective against herpes simplex virus (HSV-1) replication. We found that archangiumide did not affect host cell viability, nor pathogen infectivity, but suppressed HSV-1 early replication, in terms of early replication genes, such as ICP0, ICP4, etc. Further scrutinizing the underlined master regulator, we found that HSV-1 VP16 protein expression was inhibited by archangiumide, as well as VP16 nuclear translocation. As VP16 is a coactivator of transcription, archangiumide harnessed the master regulator of HSV-1 early replication. Together, here we provide evidence that allene macrolide archangiumide possesses robust antiviral functions that may be valuable for a novel viral infection intervention, as macrolides are generally safe drugs for prolonged treatments.