Preclinical Profile and Characterization of the Hepatitis B Virus Core Protein Inhibitor ABI-H0731.

ABSTRACT: ABI-H0731, a first-generation hepatitis B virus (HBV) core protein inhibitor, has demonstrated effective antiviral activity in chronic hepatitis B (CHB) patients in a phase 1b clinical trial and is currently being further evaluated in phase 2 clinical trials. Here, we report the preclinical profile of ABI-H0731. In in vitro cell culture systems (HepG2-derived cell lines HepAD38 and HepG2-NTCP and primary human hepatocytes [PHHs]), ABI-H0731 exhibited selective inhibition of HBV DNA replication (50% effective concentration [EC₅₀] from 173 nM to 307 nM). Most importantly, ABI-H0731 suppressed covalently closed circular DNA (cccDNA) formation in two de novo infection models with EC₅₀s from 1.84 μM to 7.3 μM. Mechanism-of-action studies indicated that ABI-H0

SUBMITTER: Huang Q 

PROVIDER: S-EPMC7577125 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature