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© Research
Publication : Antimicrobial agents and chemotherapy

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

Team: Group: Humanized mice for infectious disease modeling
Team: Innate Immunity
Team: U1223 – Pathophysiology of the immune system
Member: Hélène Strick-Marchand
Member: James Di Santo
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Antimicrobial agents and chemotherapy - 27 Jan 2020

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

Link to DOI – e01701-1910.1128/AAC.01701-19

Antimicrob Agents Chemother 2020 01; 64(2):

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.