# Early Intervention in Herpes Simplex Virus-1 Replication in Vitro with Allenic Macrolide Archangiumide

## TL;DR

A new natural compound called archangiumide can stop the early replication of herpes simplex virus-1 without harming host cells.

## Contribution

Archangiumide is shown to inhibit HSV-1 replication by targeting the VP16 protein, a key regulator of viral transcription.

## Key findings

- Archangiumide suppresses HSV-1 early replication genes like ICP0 and ICP4.
- The compound inhibits VP16 protein expression and its nuclear translocation.
- Archangiumide does not affect host cell viability or pathogen infectivity.

## 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.