A New Role for Capsid Assembly Modulators To Target Mature Hepatitis B Virus Capsids and Prevent Virus Infection.
Allosteric Regulation
/ genetics
Antiviral Agents
/ pharmacology
Blotting, Southern
Capsid
/ chemistry
DNA, Circular
/ genetics
Escherichia coli
/ genetics
Hep G2 Cells
Hepatitis B
/ drug therapy
Hepatitis B virus
/ drug effects
Humans
Microscopy, Electron, Transmission
Pyrimidines
/ chemistry
Viral Core Proteins
/ genetics
antiviral agents
capsid
core protein
core protein allosteric modulators
covalently closed circular DNA
hepatitis B virus
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
20 12 2019
20 12 2019
Historique:
received:
21
07
2019
accepted:
18
10
2019
pubmed:
30
10
2019
medline:
1
9
2020
entrez:
30
10
2019
Statut:
epublish
Résumé
Hepatitis B virus (HBV) is a major human pathogen, killing an estimated 887,000 people per year. Therefore, potentially curative therapies are of high importance. Following infection, HBV deposits a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that serves as a transcription template and is not affected by current therapies. HBV core protein allosteric modulators (CpAMs) prevent correct capsid assembly but may also affect early stages of HBV infection. In this study, we aimed to determine the antiviral efficacy of a novel, structurally distinct heteroaryldihydropyrimidine (HAP)-type CpAM, HAP_R01, and investigated whether and how HAP_R01 prevents the establishment of HBV infection. HAP_R01 shows a significant inhibition of cccDNA formation when applied during the first 48 h of HBV infection. Inhibiting cccDNA formation, however, requires >1-log
Identifiants
pubmed: 31658963
pii: AAC.01440-19
doi: 10.1128/AAC.01440-19
pmc: PMC7187577
pii:
doi:
Substances chimiques
Antiviral Agents
0
DNA, Circular
0
Pyrimidines
0
Viral Core Proteins
0
heteroaryldihydropyrimidine
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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