Asiatic acid inhibits HBV cccDNA transcription by promoting HBx degradation.
Animals
Hepatitis B virus
/ drug effects
Pentacyclic Triterpenes
/ pharmacology
Viral Regulatory and Accessory Proteins
/ metabolism
Mice
Trans-Activators
/ metabolism
Humans
DNA, Circular
/ genetics
Antiviral Agents
/ pharmacology
DNA, Viral
/ genetics
Transcription, Genetic
/ drug effects
Disease Models, Animal
Virus Replication
/ drug effects
Proteolysis
/ drug effects
Hepatitis B
/ virology
Asiatic acid
HBx
Hepatitis B virus
Journal
Virology journal
ISSN: 1743-422X
Titre abrégé: Virol J
Pays: England
ID NLM: 101231645
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
17
06
2024
accepted:
13
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Hepatitis B virus (HBV) infection is a persistent global public health problem, and curing for chronic hepatitis B (CHB) through the application of existing antiviral drugs is beset by numerous challenges. The viral protein HBx is a critical regulatory factor in the life cycle of HBV. Targeting HBx is a promising possibility for the development of novel therapeutic strategies. The Nano-Glo Asiatic acid, an extract of Centella asiatica, significantly reduced the HBx level. Mechanistic studies demonstrated that asiatic acid may promote the degradation of HBx in an autophagy pathway-dependent manner. Subsequently, asiatic acid was found to reduce the amount of HBx bound to covalently closed circular DNA (cccDNA) microchromosomes, and repressive chromatin modifications then occurred, ultimately inhibiting cccDNA transcriptional activity. Moreover, in HBV-infected cells and a mouse model of persistent HBV infection, asiatic acid exhibited potent anti-HBV activity, as evidenced by decreased levels of HBV RNAs, HBV DNA and HBsAg. Asiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent.
Sections du résumé
BACKGROUND
BACKGROUND
Hepatitis B virus (HBV) infection is a persistent global public health problem, and curing for chronic hepatitis B (CHB) through the application of existing antiviral drugs is beset by numerous challenges. The viral protein HBx is a critical regulatory factor in the life cycle of HBV. Targeting HBx is a promising possibility for the development of novel therapeutic strategies.
METHODS
METHODS
The Nano-Glo
RESULTS
RESULTS
Asiatic acid, an extract of Centella asiatica, significantly reduced the HBx level. Mechanistic studies demonstrated that asiatic acid may promote the degradation of HBx in an autophagy pathway-dependent manner. Subsequently, asiatic acid was found to reduce the amount of HBx bound to covalently closed circular DNA (cccDNA) microchromosomes, and repressive chromatin modifications then occurred, ultimately inhibiting cccDNA transcriptional activity. Moreover, in HBV-infected cells and a mouse model of persistent HBV infection, asiatic acid exhibited potent anti-HBV activity, as evidenced by decreased levels of HBV RNAs, HBV DNA and HBsAg.
CONCLUSIONS
CONCLUSIONS
Asiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent.
Identifiants
pubmed: 39468627
doi: 10.1186/s12985-024-02535-3
pii: 10.1186/s12985-024-02535-3
doi:
Substances chimiques
asiatic acid
9PA5A687X5
Pentacyclic Triterpenes
0
Viral Regulatory and Accessory Proteins
0
Trans-Activators
0
hepatitis B virus X protein
0
DNA, Circular
0
Antiviral Agents
0
DNA, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
268Subventions
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : National Natural Science Foundation of China
ID : 82372996
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : the Chongqing Natural Science Foundation
ID : CSTB2022NSCQ-MSX0864, CSTB2023NSCQ-BHX0170, cstc2021jcyj-bshX0179, CSTB2023NSCQ-MSX0480
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Sci-ence and Technology Research Project of Chongqing Municipal Education Commis-sion
ID : KJQN202100429, KJQN202300483
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Organisme : Future Medical Youth Innovation Team of Chongqing Medical University
ID : W0040
Informations de copyright
© 2024. The Author(s).
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