Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity.

ABSTRACT:

Background & aims

The sodium taurocholate co-transporting polypeptide (NTCP) is the main target of most hepatitis B virus (HBV) specific entry inhibitors. Unfortunately, these agents also block NTCP transport of bile acids into hepatocytes, and thus have the potential to cause adverse effects. We aimed to identify small molecules that inhibit HBV entry while maintaining NTCP transporter function.

Methods

We characterized a series of cyclosporine (CsA) derivatives for their anti-HBV activity and NTCP binding specificity using HepG2 cells overexpressing NTCP and primary human hepatocytes. The four most potent derivatives were tested for their capacity to prevent HBV entry, but maintain NTCP transporter function. Their antiviral activity against different HBV genotypes was anal

SUBMITTER: Shimura S 

PROVIDER: S-EPMC7172969 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature