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Discovery and structure activity relationship of glyoxamide derivatives as anti-hepatitis B virus agents.

ABSTRACT: Chronic hepatitis B viral infection is a significant health problem world-wide, and currently available antiviral agents suppress HBV infections, but rarely cure this disease. It is presumed that antiviral agents that target the viral nuclear reservoir of transcriptionally active cccDNA may eliminate HBV infection. Through a series of chemical optimization, we identified a new series of glyoxamide derivatives affecting HBV nucleocapsid formation and cccDNA maintenance at low nanomolar levels. Among all the compounds synthesized, GLP-26 displays a major effect on HBV DNA, HBeAg secretion and cccDNA amplification. In addition, GLP-26 shows a promising pre-clinical profile and long-term effect on viral loads in a humanized mouse model.

SUBMITTER: Amblard F

PROVIDER: S-EPMC7856252 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Discovery and structure activity relationship of glyoxamide derivatives as anti-hepatitis B virus agents.

Amblard Franck F Boucle Sebastien S Bassit Leda L Chen Zhe Z Sari Ozkan O Cox Bryan B Verma Kiran K Ozturk Tugba T Ollinger-Russell Olivia O Schinazi Raymond F RF

Bioorganic & medicinal chemistry 20201216

Chronic hepatitis B viral infection is a significant health problem world-wide, and currently available antiviral agents suppress HBV infections, but rarely cure this disease. It is presumed that antiviral agents that target the viral nuclear reservoir of transcriptionally active cccDNA may eliminate HBV infection. Through a series of chemical optimization, we identified a new series of glyoxamide derivatives affecting HBV nucleocapsid formation and cccDNA maintenance at low nanomolar levels. Am ...[more]

PMID: 33421915

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