Disruption of the NTCP-EGFR receptor complex as a strategy for selective inhibition of hepatitis B and D virus entry.

Oxy229 disrupts the NTCP–EGFR receptor complex and selectively blocks HBV and HDV entry into HepG2-NTCP cells and primary human hepatocytes.

• Why it matters: HBV and HDV rely on coordinated receptor interactions for hepatocyte entry, but targeting this specific NTCP–EGFR machinery could improve antiviral selectivity.
• What they did: The authors built an in vitro assay for NTCP–EGFR interaction and found Oxy229, an oxysterol-based compound, that disrupts the interaction and impairs HBV-NTCP relocalization from the plasma membrane to intracellular vesicles.
• The result: Oxy229 inhibited HBV/HDV infection without compromising NTCP bile acid transport or EGFR downstream Ras-MAPK and PI3K-Akt signaling, and a derivative, Oxy283, also inhibited NTCP multimerization to enhance anti-HBV potency.

AI summary of the abstract · may contain errors · not medical advice · read the paper.