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© Research
Publication : Antimicrobial agents and chemotherapy

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Antimicrobial agents and chemotherapy - 11 Nov 2019

Amblard F, Boucle S, Bassit L, Cox B, Sari O, Tao S, Chen Z, Ozturk T, Verma K, Russell O, Rat V, de Rocquigny H, Fiquet O, Boussand M, Di Santo J, Strick-Marchand H, Schinazi RF

Link to Pubmed [PMID] – 31712213

Antimicrob. Agents Chemother. 2019 Nov;

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 and inhibition of HBeAg secretion, and reduced cccDNA amplification in addition to a promising pre-clinical profile. Strikingly, long term combination treatment with entecavir in a humanized mouse model induced decrease in viral loads and viral antigens that was sustained for up to 12 weeks after treatment cessation.

https://www.ncbi.nlm.nih.gov/pubmed/31712213