About: HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways

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About: HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways
Creator	Li, Wenhui Qi, Yonghe Chang, Jinhong Cheng, Junjun Cuconati, Andrea Du, Yanming Guo, Fang Guo, Ju-Tao Sheraz, Muhammad Su, Qing Wei, Lai Zhao, Qiong Cheng, Sheraz
Source	PMC
abstract	Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or “empty” capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.
has issue date	2017-09-25(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1006658
bibo:pmid	28945802
has license	cc-by
sha1sum (hex)	ee019cb6808f738c245cc9de12b08a19951ef594
schema:url	https://doi.org/10.1371/journal.ppat.1006658
resource representing a document's title	HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways
has PubMed Central identifier	PMC5629035
has PubMed identifier	28945802
schema:publication	PLoS Pathog
resource representing a document's body	covid:ee019cb6808f738c245cc9de12b08a19951ef594#body_text
is schema:about of	named entity 'reverse' named entity 'studies' named entity 'cccDNA' named entity 'hepatitis B' named entity 'dual' named entity 'modulate' named entity 'discovery' named entity 'nucleocapsids' named entity 'SBAs' named entity 'core' named entity 'DNA replication' named entity 'derived' named entity 'nucleocapsid' named entity 'HBV' named entity 'PROTEIN ' named entity 'DE NOVO' named entity 'CITATION' named entity 'PATHWAYS' named entity 'DNA' named entity 'DNA REPLICATION' named entity 'KINETICS' named entity 'PROGENY' named entity 'DISASSEMBLY' named entity 'RESULTING IN' named entity 'PRE' named entity 'MODULATORS' named entity 'TRANSCRIPTIONAL' named entity 'AMPLIFICATION' named entity 'PROTEIN ASSEMBLY' named entity 'DISCOVERY' named entity 'TAKE PLACE' named entity 'ITS' named entity 'DERIVED' named entity 'TO TAKE' named entity 'VIRIONS' named entity 'CLOSED' named entity 'ADDITION' named entity 'DUAL' named entity 'RNA' named entity 'TARGETING' named entity 'CCCDNA' named entity 'PREVENTS' named entity 'VIRAL DNA' named entity 'FORMATION' named entity 'MATURE' named entity 'UNDERLYING' named entity 'PROTEIN ' named entity 'STUDIES' named entity 'CHRONIC HEPATITIS B' named entity 'HAVE' named entity 'INCLUDING' named entity 'UNDERSTANDING' named entity 'VIRAL' named entity 'CYTOPLASM' named entity 'NUCLEOCAPSID' named entity 'SYNTHESIS' named entity 'HEPATITIS B VIRUS' named entity 'HAPS' named entity 'SUPPRESS' named entity 'CONTAINING' named entity 'INTRACELLULAR' named entity 'ELONGATION' named entity 'PATHWAYS' named entity 'AMPLIFICATION' named entity 'DNA POLYMERASE' named entity 'ABILITY' named entity 'DOUBLE-STRANDED DNA' named entity 'VIRAL GENOME REPLICATION' named entity 'SMALL MOLECULES'

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