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Antiviral Res. 2020 May 4:104815. doi: 10.1016/j.antiviral.2020.104815. [Epub ahead of print]
HBV replication inhibitors.
Rouviere CP1, Dousson CB2, Tavis JE3.
Author information
1
Ai-biopharma, Medicinal Chemistry Department, Montpellier, France.
2
Ai-biopharma, Medicinal Chemistry Department, Montpellier, France. Electronic address: [email protected].
3
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO, USA. Electronic address: [email protected].
Abstract
Chronic Hepatitis B Virus infections afflict >250 million people and kill nearly 1 million annually. Current non-curative therapies are dominated by nucleos(t)ide analogs (NAs) that profoundly but incompletely suppress DNA synthesis by the viral reverse transcriptase. Residual HBV replication during NA therapy contributes to maintenance of the critical nuclear reservoir of the HBV genome, the covalently-closed circular DNA, and to ongoing infection of naive cells. Identification of next-generation NAs with improved efficacy and safety profiles, often through novel prodrug approaches, is the primary thrust of ongoing efforts to improve HBV replication inhibitors. Inhibitors of the HBV ribonuclease H, the other viral enzymatic activity essential for viral genomic replication, are in preclinical development. The complexity of HBV's reverse transcription pathway offers many other potential targets. HBV's protein-priming of reverse transcription has been briefly explored as a potential target, as have the host chaperones necessary for function of the HBV reverse transcriptase. Improved inhibitors of HBV reverse transcription would reduce HBV's replication-dependent persistence mechanisms and are therefore expected to become a backbone of future curative combination anti-HBV therapies.
Copyright © 2020 Elsevier B.V. All rights reserved.
KEYWORDS:
Chronic hepatitis B; Hepatitis B virus; Nucleos(t)ide analogs; Reverse transcriptase inhibitors; Ribonuclease H inhibitors
PMID:
32380149
DOI:
10.1016/j.antiviral.2020.104815 |
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