# Onnamides A and B Suppress Hepatitis B Virus Transcription by Inhibiting Viral Promoter Activity

## TL;DR

Onnamides A and B, natural compounds from a marine sponge, inhibit hepatitis B virus transcription and could be potential treatments.

## Contribution

The study reveals onnamides A and B as potent inhibitors of HBV RNA transcription through suppression of viral promoter activity.

## Key findings

- Onnamides A and B significantly reduce HBV RNA levels, especially pregenomic RNA.
- The compounds inhibit HBV transcription driven by the core and X promoters.
- Onnamides show anti-HBV activity without affecting virus binding, entry, or DNA formation.

## Abstract

We recently reported that onnamide A, a marine-derived natural compound isolated from the sponge Theonella sp., inhibits the entry process of SARS-CoV-2 infection. However, its antiviral activity against other viruses remains largely unexplored. Here, we investigated the effects of onnamide A and its structurally related analog, onnamide B, on hepatitis B virus (HBV) infection. Using iNTCP cells, a hepatoblastoma-derived cell line permissive to HBV infection, we found that onnamides A and B exhibited cytotoxicity, with CC50 values of 0.53 ± 0.10 μM and 2.37 ± 0.25 μM, respectively. Following HBV infection, the levels of total HBV RNA were significantly reduced by onnamide A (IC50 = 0.06 ± 0.01 μM) and onnamide B (IC50 = 0.23 ± 0.06 μM). Notably, both compounds markedly decreased the levels of HBV pregenomic RNA. Furthermore, significant inhibition was particularly evident when onnamide treatment was initiated after HBV infection. Consistent with these observations, onnamides did not affect HBV binding, entry, or covalently closed circular DNA formation, but they significantly suppressed HBV RNA transcription. In particular, the transcriptional activities driven by the core and X promoters were markedly inhibited by onnamide treatment. Taken together, our findings demonstrate that onnamides possess potent anti-HBV activity and highlight their potential as candidate compounds targeting HBV RNA transcription.