keyword
MENU ▼
Read by QxMD icon Read
search

HBV capsid

keyword
https://www.readbyqxmd.com/read/29906396/synthesis-and-evaluation-of-n-phenyl-3-sulfamoyl-benzamide-derivatives-as-capsid-assembly-modulators-inhibiting-hepatitis-b-virus-hbv
#1
Koen Vandyck, Geert Rombouts, Bart Stoops, Abdellah Tahri, Ann Vos, Wim Verschueren, Yiming Wu, Jingmei Yang, Fuliang Hou, Bing Huang, Karen Vergauwen, Pascale Dehertogh, Jan-Martin Berke, Pierre Jean Marie Bernard Raboisson
Small molecule induced Hepatitis B virus (HBV) capsid assembly modulation is considered an attractive approach for new antiviral therapies against HBV. Here we describe efforts towards the discovery of a HBV capsid assembly modulator in a hit-to-lead optimization, resulting in JNJ-632, a tool compound used to further profile the mode of action. Administration of JNJ-632 (54) in HBV genotype D infected chimeric mice, resulted in a 2.77 log reduction of the HBV DNA viral load.
June 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29869263/displaying-whole-chain-proteins-on-hepatitis-b-virus-capsid-like-particles
#2
Julia Heger-Stevic, Philipp Kolb, Andreas Walker, Michael Nassal
The highly immunogenic icosahedral capsid of hepatitis B virus (HBV) can be exploited as a nanoparticulate display platform for heterologous molecules. Its constituent core protein (HBc) of only ~180 amino acids spontaneously forms capsid-like particles (CLPs) even in E. coli. The immunodominant c/e1 epitope in the center of the HBc primary sequence comprises a solvent-exposed loop that tolerates insertions of flexible peptide sequences yet also of selected whole proteins as long as their 3D structures fit into the two acceptor sites...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29782550/multiple-roles-of-core-protein-linker-in-hepatitis-b-virus-replication
#3
Kuancheng Liu, Laurie Luckenbaugh, Xiaojun Ning, Ji Xi, Jianming Hu
Hepatitis B virus (HBV) core protein (HBc) contains an N-terminal domain (NTD, assembly domain) and a C-terminal domain (CTD), which are linked by a flexible linker region. HBc plays multiple essential roles in viral replication, including capsid assembly, packaging of the viral pregenomic RNA (pgRNA) into nucleocapsids, viral reverse transcription that converts pgRNA to the genomic DNA, and secretion of DNA-containing (complete) virions or genome-free (empty) virions. The HBc linker is generally assumed to act merely as a spacer between NTD and CTD but some results suggest that the linker may affect NTD assembly...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29770355/host-regulated-hepatitis-b-virus-capsid-assembly-in-a-mammalian-cell-free-system
#4
Kuancheng Liu, Jianming Hu
The hepatitis B virus (HBV) is an important global human pathogen and represents a major cause of hepatitis, liver cirrhosis and liver cancer. The HBV capsid is composed of multiple copies of a single viral protein, the capsid or core protein (HBc), plays multiple roles in the viral life cycle, and has emerged recently as a major target for developing antiviral therapies against HBV infection. Although several systems have been developed to study HBV capsid assembly, including heterologous overexpression systems like bacteria and insect cells, in vitro assembly using purified protein, and mammalian cell culture systems, the requirement for non-physiological concentrations of HBc and salts and the difficulty in manipulating host regulators of assembly presents major limitations for detailed studies on capsid assembly under physiologically relevant conditions...
April 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29743374/common-and-distinct-capsid-and-surface-protein-requirements-for-secretion-of-complete-and-genome-free-hepatitis-b-virions
#5
Xiaojun Ning, Laurie Luckenbaugh, Kuancheng Liu, Volker Bruss, Camille Sureau, Jianming Hu
During the morphogenesis of hepatitis B virus (HBV), an enveloped virus, two types of virions are secreted: (1) a minor population of complete virions containing a mature nucleocapsid with the characteristic, partially double-stranded, relaxed circular DNA genome and (2) a major population containing an empty capsid with no DNA or RNA (empty virions). Secretion of both types of virions requires interactions between the HBV capsid or core protein (HBc) and the viral surface or envelope proteins. We have studied the requirements from both HBc and envelope proteins for empty virion secretion, in comparison with those for secretion of complete virions...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29714713/molecular-jenga-the-percolation-phase-transition-collapse-in-virus-capsids
#6
Nicholas Brunk, Lye Siang Lee, James A Glazier, William D Butske, Adam Zlotnick
Virus capsids are polymeric protein shells that protect the viral cargo. About half of known virus families have icosahedral capsids that self-assemble from tens to thousands of subunits. Capsid disassembly is critical to the lifecycles of many viruses yet is poorly understood. Here, we apply a graph and percolation theory to examine the effect of removing capsid subunits on capsid stability and fragmentation. Based on the structure of the icosahedral capsid of Hepatitis B Virus (HBV), we constructed a graph of rhombic subunits arranged with icosahedral symmetry...
May 1, 2018: Physical Biology
https://www.readbyqxmd.com/read/29708733/characterization-of-virus-capsids-and-their-assembly-intermediates-by-multi-cycle-resistive-pulse-sensing-with-four-pores-in-series
#7
Jinsheng Zhou, Panagiotis Kondylis, Daniel G Haywood, Zachary D Harms, Lye Siang Lee, Adam Zlotnick, Stephen C Jacobson
Virus self-assembly is a critical step in the virus lifecycle. Understanding how viruses assemble and disassemble provides needed insight into developing antiviral pharmaceuticals. Few tools offer sufficient resolution to study assembly intermediates that differ in size by a few dimers. Our goal is to improve resistive-pulse sensing on nanofluidic devices to offer better particle-size and temporal resolution to study intermediates and capsids generated along the assembly pathway. To increase the particle-size resolution of the resistive-pulse technique, we measured the same, single virus particles up to a thousand times, cycling them back and forth across a series of nanopores by switching the polarity of the applied potential, i...
April 30, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29708495/all-atom-molecular-dynamics-of-the-hbv-capsid-reveals-insights-into-biological-function-and-cryo-em-resolution-limits
#8
Jodi A Hadden, Juan R Perilla, Christopher John Schlicksup, Balasubramanian Venkatakrishnan, Adam Zlotnick, Klaus Schulten
The hepatitis B virus capsid represents a promising therapeutic target. Experiments suggest the capsid must be flexible to function; however, capsid structure and dynamics have not been thoroughly characterized in the absence of icosahedral symmetry constraints. Here, all-atom molecular dynamics simulations are leveraged to investigate the capsid without symmetry bias, enabling study of capsid flexibility and its implications for biological function and cryo-EM resolution limits. Simulation results confirm flexibility and reveal a propensity for asymmetric distortion...
April 27, 2018: ELife
https://www.readbyqxmd.com/read/29679386/hepatitis-b-virus-evasion-from-cgas-sensing-in-human-hepatocytes
#9
Eloi R Verrier, Seung-Ae Yim, Laura Heydmann, Houssein El Saghire, Charlotte Bach, Vincent Turon-Lagot, Laurent Mailly, Sarah C Durand, Julie Lucifora, David Durantel, Patrick Pessaux, Nicolas Manel, Ivan Hirsch, Mirjam B Zeisel, Nathalie Pochet, Catherine Schuster, Thomas F Baumert
Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and cancer worldwide. The mechanisms of viral genome sensing and the evasion of innate immune responses by HBV infection are still poorly understood. Recently, the cyclic GMP-AMP synthase (cGAS) was identified as a DNA sensor. In this study, we aimed to investigate the functional role of cGAS in sensing of HBV infection and elucidate the mechanisms of viral evasion. We performed functional studies including loss- and gain-of-function experiments combined with cGAS effector gene expression profiling in an infectious cell culture model, primary human hepatocytes and HBV-infected human liver chimeric mice...
April 20, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29672035/multiple-pathways-in-capsid-assembly
#10
Corinne A Lutomski, Nicholas A Lyktey, Elizabeth E Pierson, Zhongchao Zhao, Adam Zlotnick, Martin F Jarrold
For a three-dimensional structure to spontaneously self-assemble from many identical components, the steps on the pathway must be kinetically accessible. Many virus capsids are icosahedral and assembled from hundreds of identical proteins, but how they navigate the assembly process is poorly understood. Capsid assembly is thought to involve stepwise addition of subunits to a growing capsid fragment. Coarse-grained models suggest that the reaction occurs on a downhill energy landscape, so intermediates are expected to be fleeting...
May 2, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29669885/the-heteroaryldihydropyrimidine-bay-38-7690-induces-hepatitis-b-virus-core-protein-aggregates-associated-with-promyelocytic-leukemia-nuclear-bodies-in-infected-cells
#11
Andrew D Huber, Jennifer J Wolf, Dandan Liu, Anna T Gres, Jing Tang, Kelsey N Boschert, Maritza N Puray-Chavez, Dallas L Pineda, Thomas G Laughlin, Emily M Coonrod, Qiongying Yang, Juan Ji, Karen A Kirby, Zhengqiang Wang, Stefan G Sarafianos
Heteroaryldihydropyrimidines (HAPs) are compounds that inhibit hepatitis B virus (HBV) replication by modulating viral capsid assembly. While their biophysical effects on capsid assembly in vitro have been previously studied, the effect of HAP treatment on capsid protein (Cp) in individual HBV-infected cells remains unknown. We report here that the HAP Bay 38-7690 promotes aggregation of recombinant Cp in vitro and causes a time- and dose-dependent decrease of Cp in infected cells, consistent with previously studied HAPs...
April 25, 2018: MSphere
https://www.readbyqxmd.com/read/29669831/hepatitis-b-virus-core-protein-dephosphorylation-occurs-during-pregenomic-rna-encapsidation
#12
Qiong Zhao, Zhanying Hu, Junjun Cheng, Shuo Wu, Yue Luo, Jinhong Chang, Jianming Hu, Ju-Tao Guo
Hepatitis B virus (HBV) core protein consists of N-terminal assembly domain and C-terminal domain (CTD) with seven conserved serines or threonine that are dynamically phosphorylated/dephosphorylated during the viral replication cycle. Sulfamoylbenzaminde derivatives are small molecular core protein allosteric modulators (CpAMs) that bind to the HAP pocket between the core protein dimer-dimer interfaces. CpAM binding alters the kinetics and pathway of capsid assembly and can result in the formation of morphologically "normal" capsids devoid of viral pregenomic (pg) RNA and DNA polymerase...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29555628/preclinical-profile-of-ab-423-an-inhibitor-of-hepatitis-b-virus-pgrna-encapsidation
#13
Nagraj Mani, Andrew G Cole, Janet R Phelps, Andrzej Ardzinski, Kyle D Cobarrubias, Andrea Cuconati, Bruce D Dorsey, Ellen Evangelista, Kristi Fan, Fang Guo, Haitao Guo, Ju-Tao Guo, Troy O Harasym, Salam Kadhim, Steven G Kultgen, Amy C H Lee, Alice H L Li, Quanxin Long, Sara A Majeski, Richeng Mao, Kevin D McClintock, Stephen P Reid, Rene Rijnbrand, Nicholas M Snead, Holly M Micolochick Steuer, Kim Stever, Sunny Tang, Xiaohe Wang, Qiong Zhao, Michael J Sofia
AB-423 is a sulfamoylbenzamide (SBA) class of HBV capsid inhibitor in Phase 1 clinical trials. In cell culture models AB-423 showed potent inhibition of HBV replication (EC50 /EC90 = 0.08-0.27 μM/0.33-1.32 μM) with no significant cytotoxicity (CC50 >10 μM). Addition of 40% human serum resulted in a 5-fold increase in the EC50 values. AB-423 inhibited HBV genotypes A through D and nucleos/tide-resistant variants in vitro Treatment of HepDES19 cells with AB-423 resulted in capsid particles devoid of encapsidated pgRNA and rcDNA indicating it is a class II capsid inhibitor...
March 19, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29542854/localizing-conformational-hinges-by-nmr-where-do-hepatitis-b-virus-core-proteins-adapt-for-capsid-assembly
#14
Lauriane Lecoq, Shishan Wang, Thomas Wiegand, Stéphane Bressanelli, Michael Nassal, Beat H Meier, Anja Böckmann
The hepatitis B virus (HBV) icosahedral nucleocapsid is assembled from 240 chemically identical core protein molecules and, structurally, comprises four groups of symmetrically nonequivalent subunits. We show here that this asymmetry is reflected in solid-state NMR spectra of the capsids, in which peak splitting is observed for a subset of residues. We compare this information to dihedral angle variations from available 3D structures and also to computational predictions of "dynamic" domains and molecular hinges...
March 15, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/29500037/hepatitis-b-virus
#15
Chiaho Shih, Ching-Chun Yang, Gansukh Choijilsuren, Chih-Hsu Chang, An-Ting Liou
This infographic about hepatitis B virus explores its replication cycle, natural history of infection and pathogenesis, and how this can be controlled and treated. Hepatitis B virus (HBV) is a common worldwide blood-borne pathogen. Chronic hepatitis B can progress to an inactive carrier state, and then, in some patients, give rise to cirrhosis and cancer of the liver, leading to death. An HBV surface-antigen vaccine is effective, but treatments are currently not curative. HBV replicates via reverse transcription...
April 2018: Trends in Microbiology
https://www.readbyqxmd.com/read/29491156/asymmetric-modification-of-hepatitis-b-virus-hbv-genomes-by-an-endogenous-cytidine-deaminase-inside-hbv-cores-informs-a-model-of-reverse-transcription
#16
Smita Nair, Adam Zlotnick
Cytidine deaminases inhibit replication of a broad range of DNA viruses by deaminating cytidines on single-stranded DNA (ssDNA) to generate uracil. While several lines of evidence have revealed hepatitis B virus (HBV) genome editing by deamination, it is still unclear which nucleic acid intermediate of HBV is modified. Hepatitis B virus has a relaxed circular double-stranded DNA (rcDNA) genome that is reverse transcribed within virus cores from a RNA template. The HBV genome also persists as covalently closed circular DNA (cccDNA) in the nucleus of an infected cell...
May 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29447911/fluorescent-protein-tagged-hepatitis-b-virus-capsid-protein-with-long-glycine-serine-linker-that-supports-nucleocapsid-formation
#17
Jiang-Yan Chen, Chun-Yang Gan, Xue-Fei Cai, Wen-Lu Zhang, Quan-Xin Long, Xia-Fei Wei, Yuan Hu, Ni Tang, Juan Chen, Haitao Guo, Ai-Long Huang, Jie-Li Hu
Fusion core proteins of Hepatitis B virus can be used to study core protein functions or capsid trafficking. A problem in constructing fusion core proteins is functional impairment of the individual domains in these fusion proteins, might due to structural interference. We reported a method to construct fusion proteins of Hepatitis B virus core protein (HBc) in which the functions of fused domains were partially kept. This method follows two principles: (1) fuse heterogeneous proteins at the N terminus of HBc; (2) use long Glycine-serine linkers between the two domains...
May 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/29427479/towards-hbv-curative-therapies
#18
REVIEW
Raymond F Schinazi, Maryam Ehteshami, Leda Bassit, Tarik Asselah
Tremendous progress has been made over the last 2 decades to discover and develop approaches to control hepatitis B virus (HBV) infections and to prevent the development of hepatocellular carcinoma using various interferons and small molecules as antiviral agents. However, none of these agents have significant impact on eliminating HBV from infected cells. Currently the emphasis is on silencing or eliminating cccDNA, which could lead to a cure for HBV. Various approaches are being developed including the development of capsid effectors, CRISPR/Cas9, TALENS, siRNA, entry and secretion inhibitors, as well as immunological approaches...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29381358/3-r-4-r-6-2-bromo-4-fluorophenyl-5-ethoxycarbonyl-2-thiazol-2-yl-3-6-dihydropyrimidin-4-yl-methyl-morpholin-2-yl-propanoic-acid-hec72702-a-novel-hepatitis-b-virus-capsid-inhibitor-based-on-clinical-candidate-gls4
#19
Qingyun Ren, Xinchang Liu, Guanghua Yan, Biao Nie, Zhifu Zou, Jing Li, Yunfu Chen, Yu Wei, Jianzhou Huang, Zhonghua Luo, Baohua Gu, Siegfried Goldmann, Jiancun Zhang, Yingjun Zhang
The inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. On the basis of the preclinical properties and clinical results of GLS4, we carried out further investigation to seek a better candidate compound with appropriate anti-HBV potency, reduced hERG activity, decreased CYP enzyme induction, and improved pharmacokinetic (PK) properties. To this end, we have successfully found that morpholine carboxyl analogues with comparable anti-HBV activities to that of GLS4 showed decreased hERG activities, but they displayed strong CYP3A4 induction in a concentration-dependent manner, except for morpholine propionic acid analogues...
February 8, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29377794/hepatitis-b-virus-core-protein-allosteric-modulators-can-distort-and-disrupt-intact-capsids
#20
Christopher John Schlicksup, Joseph Che-Yen Wang, Samson Francis, Balasubramanian Venkatakrishnan, William W Turner, Michael VanNieuwenhze, Adam Zlotnick
Defining mechanisms of direct-acting antivirals facilitates drug development and our understanding of virus function. Heteroaryldihydropyrimidines (HAPs) inappropriately activate assembly of hepatitis B virus (HBV) core protein (Cp), suppressing formation of virions. We examined a fluorophore-labeled HAP, HAP-TAMRA. HAP-TAMRA induced Cp assembly and also bound pre-assembled capsids. Kinetic and spectroscopic studies imply that HAP-binding sites are usually not available but are bound cooperatively. Using cryo-EM, we observed that HAP-TAMRA asymmetrically deformed capsids, creating a heterogeneous array of sharp angles, flat regions, and outright breaks...
January 29, 2018: ELife
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"