keyword
MENU ▼
Read by QxMD icon Read
search

HBV capsid

keyword
https://www.readbyqxmd.com/read/28521532/new-antivirals-for-the-treatment-of-chronic-hepatitis-b
#1
Vincent Soriano, Pablo Barreiro, Laura Benitez, Jose M Peña, Carmen de Mendoza
Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription...
May 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28492809/serum-microrna-30c-levels-are-correlated-with-disease-progression-in-xinjiang-uygur-patients-with-chronic-hepatitis-b
#2
J Zhang, J Ma, H Wang, L Guo, J Li
We aimed to investigate the potential role and mechanism of microRNA-30c (miR-30c) in the pathological development of chronic hepatitis B (CHB). The serum levels of miR-30c in hepatitis B virus (HBV) carrier Xinjiang Uygur patients with inactive, low-replicative, high-replicative and HBe antigen-positive CHB were investigated. HepG2 cells were co-transfected with pHBV1.3 and miR-30c mimic or inhibitor or scramble RNA. The effects of miR-30c dysregulation on HBV replication and gene expression, cell proliferation and cell cycle were then investigated...
May 4, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28469174/allosteric-conformational-changes-of-human-hbv-core-protein-transform-its-assembly
#3
Chuang Liu, Guizhen Fan, Zhao Wang, Hong-Song Chen, Chang-Cheng Yin
Hepatitis B Virus core protein (HBc) has multiple roles in the viral lifecycle: viral assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions. HBc displays assembly polymorphism - it can assemble into icosahedral capsid and aberrant non-capsid structures. It has been hypothesized that the assembly polymorphism is due to allosteric conformational changes of HBc dimer, the smallest assembly unit, however, the mechanism governing the polymorphic assembly of the HBc dimer is still elusive...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28450058/inhibition-of-hepatitis-b-virus-replication-by-n-hydroxyisoquinolinediones-and-related-polyoxygenated-heterocycles
#4
Tiffany C Edwards, Elena Lomonosova, Jenny A Patel, Qilan Li, Juan A Villa, Ankit K Gupta, Lynda A Morrison, Fabrice Bailly, Philippe Cotelle, Erofili Giannakopoulou, Grigoris Zoidis, John E Tavis
We previously reported low sensitivity of the hepatitis B virus (HBV) ribonuclease H (RNaseH) enzyme to inhibition by N-hydroxyisoquinolinedione (HID) compounds. Subsequently, our biochemical RNaseH assay was found to have a high false negative rate for predicting HBV replication inhibition, leading to underestimation of the number of HIDs that inhibit HBV replication. Here, 39 HID compounds and structurally related polyoxygenated heterocycles (POH), N-hydroxypyridinediones (HPD), and flutimides were screened for inhibition of HBV replication in vitro...
April 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28407787/glucose-regulated-protein-78-demonstrates-antiviral-effects-but-is-more-suitable-for-hepatocellular-carcinoma-prevention-in-hepatitis-b
#5
Nai Q Zheng, Zi H Zheng, Hai X Xu, Ming X Huang, Xiao M Peng
BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver cirrhosis and hepatocellular carcinoma in Asia and Africa. Existing antivirals cannot cure HBV or eliminate risk of hepatocellular carcinoma. Glucose-regulated protein 78 (GRP78) can inhibit HBV replication, but promote virion secretion and hepatocellular cancer cell invasion. For these reasons, the overall effect of GRP78 on HBV production and whether to utilize the HBV replication-inhibitory effect of GRP78 up-regulation or the hepatocellular cancer cell invasion-inhibitory effect of its down-regulation were further investigated in order to improve the efficacy of current antiviral therapy...
April 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/28401569/influences-on-viral-replication-and-sensitivity-to-gls4-a-hap-compound-of-naturally-occurring-t109-v124-mutations-in-hepatitis-b-virus-core-protein
#6
Jianghua Wang, Haiying Zhang, Yingjun Zhang, Dong Jiang, Jing Li, Siegfried Goldmann, Qingyun Ren, Ran Fei, Xueyan Wang, Lai Wei
Heteroaryldihydropyrimidine (HAP) compounds inhibit HBV replication by binding to a hydrophobic pocket at the interface between hepatitis B virus core protein (HBcAg) dimer, which interrupts capsid assembly by changing the kinetics and thermodynamics during this process. Structure biological studies have identified several amino acids in HBcAg crucial for compound binding. Here we investigated the polymorphisms of T109 and V124 amino acids in HBV sequences submitted to GenBank database. Naturally occurring T109 and V124 and/or possible compensatory mutations in neighbored amino acids were introduced into HBV-expressing plasmids...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28383274/past-current-and-future-developments-of-therapeutic-agents-for-treatment-of-chronic-hepatitis-b-virus-infection
#7
Yameng Pei, Chunting Wang, S Frank Yan, Gang Liu
For decades, treatment of hepatitis B virus (HBV) infection has been relying on interferon (IFN)-based therapies and nucleoside/nucleotide analogues (NAs) that selectively target the viral polymerase reverse transcriptase (RT) domain and thereby disrupt HBV viral DNA synthesis. We have summarized here the key steps in the HBV viral life cycle, which could potentially be targeted by novel anti-HBV therapeutics. A wide range of next-generation direct antiviral agents (DAAs) with distinct mechanisms of actions are discussed, including entry inhibitors, transcription inhibitors, nucleoside/nucleotide analogues, inhibitors of viral ribonuclease H (RNase H), modulators of viral capsid assembly, inhibitors of HBV surface antigen (HBsAg) secretion, RNA interference (RNAi) gene silencers, antisense oligonucleotides (ASOs), and natural products...
April 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28339215/discovery-and-pre-clinical-characterization-of-third-generation-4-h-heteroaryldihydropyrimidine-hap-analogues-as-hepatitis-b-virus-hbv-capsid-inhibitors
#8
Zongxing Qiu, Xianfeng Lin, Weixing Zhang, Mingwei Zhou, Lei Guo, Buelent Kocer, Guolong Wu, Zhisen Zhang, Haixia Liu, Houguang Shi, Buyu Kou, Taishan Hu, Yimin Hu, Mengwei Huang, S Frank Yan, Zhiheng Xu, Zheng Zhou, Ning Qin, Yue Fen Wang, Shuang Ren, Hongxia Qiu, Yuxia Zhang, Yi Zhang, Xiaoyue Wu, Kai Sun, Sheng Zhong, Jianxun Xie, Giorgio Ottaviani, Yuan Zhou, Lina Zhu, Xiaojun Tian, Liping Shi, Fang Shen, Yi Mao, Xue Zhou, Lu Gao, John A T Young, Jim Zhen Wu, Guang Yang, Alexander V Mayweg, Hong C Shen, Guozhi Tang, Wei Zhu
Described herein are the discovery and structure-activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters...
April 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28335554/complete-and-incomplete-hepatitis-b-virus-particles-formation-function-and-application
#9
REVIEW
Jianming Hu, Kuancheng Liu
Hepatitis B virus (HBV) is a para-retrovirus or retroid virus that contains a double-stranded DNA genome and replicates this DNA via reverse transcription of a RNA pregenome. Viral reverse transcription takes place within a capsid upon packaging of the RNA and the viral reverse transcriptase. A major characteristic of HBV replication is the selection of capsids containing the double-stranded DNA, but not those containing the RNA or the single-stranded DNA replication intermediate, for envelopment during virion secretion...
March 21, 2017: Viruses
https://www.readbyqxmd.com/read/28322548/nanofluidic-devices-with-8-pores-in-series-for-real-time-resistive-pulse-analysis-of-hepatitis-b-virus-capsid-assembly
#10
Panagiotis Kondylis, Jinsheng Zhou, Zachary D Harms, Andrew R Kneller, Lye Siang Lee, Adam Zlotnick, Stephen C Jacobson
To improve the precision of resistive-pulse measurements, we have used a focused ion beam instrument to mill nanofluidic devices with 2, 4, and 8 pores in series and compared their performance. The in-plane design facilitates the fabrication of multiple pores in series which, in turn, permits averaging of the series of pulses generated from each translocation event. The standard deviations (σ) of the pulse amplitude distributions decrease by 2.7-fold when the average amplitudes of eight pulses are compared to the amplitudes of single pulses...
April 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28228589/capsid-phosphorylation-state-and-hepadnavirus-virion-secretion
#11
Xiaojun Ning, Suresh H Basagoudanavar, Kuancheng Liu, Laurie Luckenbaugh, Duoqian Wei, Chunyan Wang, Bo Wei, Yingren Zhao, Taotao Yan, William Delaney, Jianming Hu
The C-terminal domain (CTD) of hepadnavirus core protein is involved in multiple steps of viral replication. In particular, the CTD is initially phosphorylated at multiple sites to facilitate viral RNA packaging into immature nucleocapsids (NCs) and the early stage of viral DNA synthesis. For the avian hepadnavirus duck hepatitis B virus (DHBV), CTD is dephosphorylated subsequently to facilitate the late stage of viral DNA synthesis and to stabilize NCs containing mature viral DNA. The role of CTD phosphorylation in virion secretion, if any, has remained unclear...
May 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28205569/heteroaryldihydropyrimidine-hap-and-sulfamoylbenzamide-sba-inhibit-hepatitis-b-virus-replication-by-different-molecular-mechanisms
#12
Zheng Zhou, Taishan Hu, Xue Zhou, Steffen Wildum, Fernando Garcia-Alcalde, Zhiheng Xu, Daitze Wu, Yi Mao, Xiaojun Tian, Yuan Zhou, Fang Shen, Zhisen Zhang, Guozhi Tang, Isabel Najera, Guang Yang, Hong C Shen, John A T Young, Ning Qin
Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28117723/nuclear-import-of-hepatitis-b-virus-capsids-and-genome
#13
REVIEW
Lara Gallucci, Michael Kann
Hepatitis B virus (HBV) is an enveloped pararetrovirus with a DNA genome, which is found in an up to 36 nm-measuring capsid. Replication of the genome occurs via an RNA intermediate, which is synthesized in the nucleus. The virus must have thus ways of transporting its DNA genome into this compartment. This review summarizes the data on hepatitis B virus genome transport and correlates the finding to those from other viruses.
January 21, 2017: Viruses
https://www.readbyqxmd.com/read/28094179/synthesis-and-antiviral-evaluation-of-novel-heteroarylpyrimidines-analogs-as-hbv-capsid-effectors
#14
Sebastien Boucle, Xiao Lu, Leda Bassit, Tugba Ozturk, Olivia Ollinger Russell, Franck Amblard, Steven J Coats, Raymond F Schinazi
New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.
February 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28061386/characterization-of-the-disassembly-and-reassembly-of-the-hbv-glycoprotein-surface-antigen-a-pliable-nanoparticle-vaccine-platform
#15
John R Gallagher, Udana Torian, Dustin M McCraw, Audray K Harris
While nanoparticle vaccine technology is gaining interest due to the success of vaccines like those for the human papillomavirus that is based on viral capsid nanoparticles, little information is available on the disassembly and reassembly of viral surface glycoprotein-based nanoparticles. One such particle is the hepatitis B virus surface antigen (sAg) that exists as nanoparticles. Here we show, using biochemical analysis coupled with electron microscopy, that sAg nanoparticle disassembly requires both reducing agent to disrupt intermolecular disulfide bonds, and detergent to disrupt hydrophobic interactions that stabilize the nanoparticle...
February 2017: Virology
https://www.readbyqxmd.com/read/28052622/novel-targets-for-hepatitis-b-virus-therapy
#16
REVIEW
Barbara Testoni, David Durantel, Fabien Zoulim
Treatment with either pegylated interferon-alpha (pegIFN-α) or last generation nucleos(t)ide analogues (NAs) successfully leads to serum viral load suppression in most chronically infected hepatitis B (CHB) patients, but HBsAg loss is only achieved in 10% of the cases after a 5-year follow-up. Thus, therapy must be administered long-term and it will not completely eliminate infection because of the persistent hepatitis B virus (HBV) minichromosome in infected cells, and cannot completely abolish the risk of developing severe sequelae such as cirrhosis and hepatocellular carcinoma...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27989113/optimization-and-synthesis-of-pyridazinone-derivatives-as-novel-inhibitors-of-hepatitis-b-virus-by-inducing-genome-free-capsid-formation
#17
Dong Lu, Feifei Liu, Weiqiang Xing, Xiankun Tong, Lang Wang, Yajuan Wang, Limin Zeng, Chunlan Feng, Li Yang, Jianping Zuo, Youhong Hu
The capsid of hepatitis B virus (HBV) plays a vital role in virus DNA replication. Targeting nucleocapsid function has been demonstrated as an effective approach for anti-HBV drug development. A high-throughput screening and mechanism study revealed the hit compound 4a as an HBV assembly effector (AEf), which could inhibit HBV replication by inducing the formation of HBV DNA-free capsids. The subsequent SAR study and drug-like optimization resulted in the discovery of the lead candidate 4r, with potent antiviral activity (IC50 = 0...
March 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27975317/detection-of-hepatitis-b-virus-particles-released-from-cultured-cells-by-particle-gel-assay
#18
Ran Yan, Dawei Cai, Yuanjie Liu, Haitao Guo
The culture fluid of HBV replicating cells contains a mixture of viral particles with different structural and genetic components, including enveloped infectious virions, genome-free virion, envelope-only subviral particles, and nonenveloped naked capsids. Based on their different physical and chemical properties, the enveloped and nonenveloped particles can be separated by the native agarose gel electrophoresis and transferred onto a positively charged microporous membrane, then the virus particle-associated protein components and nucleic acid content can be detected by antibody-based enzyme immunoassay (EIA) and hybridization, respectively...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27975314/measuring-changes-in-cytosolic-calcium-levels-in-hbv-and-hbx-expressing-cultured-primary-hepatocytes
#19
Jessica C Casciano, Michael J Bouchard
Chronic infection with hepatitis B virus (HBV) remains a major worldwide health concern and is the leading cause of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is the only regulatory protein encoded in the HBV genome; HBx stimulates HBV replication in vivo and in vitro. HBx also regulates cytosolic Ca(2+) signaling, and altered Ca(2+) signaling is associated with the development of many diseases, including HCC. Importantly, many HBx functions, including HBx modulation of cell proliferation, apoptosis, and transcription pathways, have been linked to changes in cytosolic Ca(2+) signaling...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27975306/intracytoplasmic-transport-of-hepatitis-b-virus-capsids
#20
Quentin Osseman, Michael Kann
The early steps of HBV entry remain largely unknown despite the recent discovery of an HBV-specific entry receptor. Following entry HBV capsids have to be transported through the cytoplasm to the nuclear periphery, followed by nuclear entry. These steps have to take place in a coordinated manner to allow delivery of the genome into the nucleus. Due to the viscosity of the cytoplasm, the intracytoplasmic translocation has to be active and directed.Here, we describe protocols that can be applied to investigations of the HBV capsid with the cytoplasmic transport systems...
2017: Methods in Molecular Biology
keyword
keyword
109360
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"