Novel Hepatitis B Virus Capsid Assembly Modulator Induces Potent Antiviral Responses and in Humanized Mice

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2019 Nov 13

PMID 31712213

Citations 31

Authors

Franck Amblard

Sebastien Boucle

Leda Bassit

Bryan Cox

Ozkan Sari

Sijia Tao

Zhe Chen

Tugba Ozturk

Kiran Verma

Olivia Russell

Virgile Rat

Hugues de Rocquigny

Oriane Fiquet

Maud Boussand

James Di Santo

Helene Strick-Marchand

Raymond F Schinazi

Affiliations

Soon will be listed here.

Abstract

Hepatitis B virus (HBV) affects an estimated 250 million chronic carriers worldwide. Though several vaccines exist, they are ineffective for those already infected. HBV persists due to the formation of covalently closed circular DNA (cccDNA)-the viral minichromosome-in the nucleus of hepatocytes. Current nucleoside analogs and interferon therapies rarely clear cccDNA, requiring lifelong treatment. Our group identified GLP-26, a novel glyoxamide derivative that alters HBV nucleocapsid assembly and prevents viral DNA replication. GLP-26 exhibited single-digit nanomolar anti-HBV activity, inhibition of HBV e antigen (HBeAg) secretion, and reduced cccDNA amplification, in addition to showing a promising preclinical profile. Strikingly, long term combination treatment with entecavir in a humanized mouse model induced a decrease in viral loads and viral antigens that was sustained for up to 12 weeks after treatment cessation.

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