Journal article

Hepatitis D Virus Entry Inhibitors Based on Repurposing Intestinal Bile Acid Reabsorption Inhibitors


Authors listKirstgen, M; Lowjaga, KAAT; Müller, SF; Goldmann, N; Lehmann, F; Glebe, D; Baringhaus, KH; Geyer, J

Publication year2021

JournalViruses

Volume number13

Issue number4

eISSN1999-4915

Open access statusGold

DOI Linkhttps://doi.org/10.3390/v13040666

PublisherMDPI


Abstract
Identification of Na+/taurocholate co-transporting polypeptide (NTCP) as high-affinity hepatic entry receptor for the Hepatitis B and D viruses (HBV/HDV) opened the field for target-based development of cell-entry inhibitors. However, most of the HBV/HDV entry inhibitors identified so far also interfere with the physiological bile acid transporter function of NTCP. The present study aimed to identify more virus-selective inhibitors of NTCP by screening of 87 propanolamine derivatives from the former development of intestinal bile acid reabsorption inhibitors (BARIs), which interact with the NTCP-homologous intestinal apical sodium-dependent bile acid transporter (ASBT). In NTCP-HEK293 cells, the ability of these compounds to block the HBV/HDV-derived preS1-peptide binding to NTCP (virus receptor function) as well as the taurocholic acid transport via NTCP (bile acid transporter function) were analyzed in parallel. Hits were subsequently validated by performing in vitro HDV infection experiments in NTCP-HepG2 cells. The most potent compounds S985852, A000295231, and S973509 showed in vitro anti-HDV activities with IC50 values of 15, 40, and 70 mu M, respectively, while the taurocholic acid uptake inhibition occurred at much higher IC50 values of 24, 780, and 490 mu M, respectively. In conclusion, repurposing of compounds from the BARI class as novel HBV/HDV entry inhibitors seems possible and even enables certain virus selectivity based on structure-activity relationships.



Citation Styles

Harvard Citation styleKirstgen, M., Lowjaga, K., Müller, S., Goldmann, N., Lehmann, F., Glebe, D., et al. (2021) Hepatitis D Virus Entry Inhibitors Based on Repurposing Intestinal Bile Acid Reabsorption Inhibitors, Viruses, 13(4), Article 666. https://doi.org/10.3390/v13040666

APA Citation styleKirstgen, M., Lowjaga, K., Müller, S., Goldmann, N., Lehmann, F., Glebe, D., Baringhaus, K., & Geyer, J. (2021). Hepatitis D Virus Entry Inhibitors Based on Repurposing Intestinal Bile Acid Reabsorption Inhibitors. Viruses. 13(4), Article 666. https://doi.org/10.3390/v13040666


Last updated on 2025-10-06 at 11:24