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Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target

Hepatitis B virus (HBV) chronically infects millions of people worldwide, which underscores the importance of discovering and designing novel anti-HBV therapeutics to complement current treatment strategies. An underexploited but attractive therapeutic target is ε, a cis-acting regulatory stem-loop...

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Autores principales: Olenginski, Lukasz T., Attionu, Solomon K., Henninger, Erica N., LeBlanc, Regan M., Longhini, Andrew P., Dayie, Theodore K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534774/
https://www.ncbi.nlm.nih.gov/pubmed/37766319
http://dx.doi.org/10.3390/v15091913
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author Olenginski, Lukasz T.
Attionu, Solomon K.
Henninger, Erica N.
LeBlanc, Regan M.
Longhini, Andrew P.
Dayie, Theodore K.
author_facet Olenginski, Lukasz T.
Attionu, Solomon K.
Henninger, Erica N.
LeBlanc, Regan M.
Longhini, Andrew P.
Dayie, Theodore K.
author_sort Olenginski, Lukasz T.
collection PubMed
description Hepatitis B virus (HBV) chronically infects millions of people worldwide, which underscores the importance of discovering and designing novel anti-HBV therapeutics to complement current treatment strategies. An underexploited but attractive therapeutic target is ε, a cis-acting regulatory stem-loop RNA situated within the HBV pregenomic RNA (pgRNA). The binding of ε to the viral polymerase protein (P) is pivotal, as it triggers the packaging of pgRNA and P, as well as the reverse transcription of the viral genome. Consequently, small molecules capable of disrupting this interaction hold the potential to inhibit the early stages of HBV replication. The rational design of such ligands necessitates high-resolution structural information for the ε–P complex or its individual components. While these data are currently unavailable for P, our recent structural elucidation of ε through solution nuclear magnetic resonance spectroscopy marks a significant advancement in this area. In this review, we provide a brief overview of HBV replication and some of the therapeutic strategies to combat chronic HBV infection. These descriptions are intended to contextualize our recent experimental efforts to characterize ε and identify ε-targeting ligands, with the ultimate goal of developing novel anti-HBV therapeutics.
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spelling pubmed-105347742023-09-29 Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target Olenginski, Lukasz T. Attionu, Solomon K. Henninger, Erica N. LeBlanc, Regan M. Longhini, Andrew P. Dayie, Theodore K. Viruses Review Hepatitis B virus (HBV) chronically infects millions of people worldwide, which underscores the importance of discovering and designing novel anti-HBV therapeutics to complement current treatment strategies. An underexploited but attractive therapeutic target is ε, a cis-acting regulatory stem-loop RNA situated within the HBV pregenomic RNA (pgRNA). The binding of ε to the viral polymerase protein (P) is pivotal, as it triggers the packaging of pgRNA and P, as well as the reverse transcription of the viral genome. Consequently, small molecules capable of disrupting this interaction hold the potential to inhibit the early stages of HBV replication. The rational design of such ligands necessitates high-resolution structural information for the ε–P complex or its individual components. While these data are currently unavailable for P, our recent structural elucidation of ε through solution nuclear magnetic resonance spectroscopy marks a significant advancement in this area. In this review, we provide a brief overview of HBV replication and some of the therapeutic strategies to combat chronic HBV infection. These descriptions are intended to contextualize our recent experimental efforts to characterize ε and identify ε-targeting ligands, with the ultimate goal of developing novel anti-HBV therapeutics. MDPI 2023-09-12 /pmc/articles/PMC10534774/ /pubmed/37766319 http://dx.doi.org/10.3390/v15091913 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Olenginski, Lukasz T.
Attionu, Solomon K.
Henninger, Erica N.
LeBlanc, Regan M.
Longhini, Andrew P.
Dayie, Theodore K.
Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target
title Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target
title_full Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target
title_fullStr Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target
title_full_unstemmed Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target
title_short Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target
title_sort hepatitis b virus epsilon (ε) rna element: dynamic regulator of viral replication and attractive therapeutic target
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10534774/
https://www.ncbi.nlm.nih.gov/pubmed/37766319
http://dx.doi.org/10.3390/v15091913
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