Capsid assembly mod 
Welcome,         Profile    Billing    Logout  
 1 Company  1 Product   1 Product   0 Diseases   2 Trials   13 News 


«123456789101112»
  • ||||||||||  Journal:  Protein phosphatase 1 catalyzes HBV core protein dephosphorylation and is co-packaged with viral pregenomic RNA into nucleocapsids. (Pubmed Central) -  Aug 27, 2020   
    Interestingly, the PP1 catalytic subunits α and β were packaged into pgRNA-containing nucleocapsids, but not empty capsids, and treatment of HBV replicating cells with core protein allosteric modulators (CpAMs) promoted empty capsid assembly and abrogated the encapsidation of PP1 α and β. Our study thus identified PP1 as a host cellular factor that is co-packaged into HBV nucleocapsids, and plays an essential role in selective packaging of the viral DNA-polymerase-pgRNA complex through catalyzing Cp dephosphorylation.
  • ||||||||||  [VIRTUAL] Identification of a new class of HBV capsid assembly modulator (On Demand Oral) -  Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_5596;    
    NVR 3-778 is a first-in-class sulfonyl carboxamide-based HBV capsid assembly modulator (CAM) that has demonstrated proof of mechanism in a Phase I clinical trial. This presentation will describe the identification and hit to lead SAR of a completely novel series of pyrazolo piperidine HBV capsid assembly modulators.
  • ||||||||||  GS CA1 / Gilead
    [VIRTUAL] Targeting HIV capsid assembly by long-acting small molecule modulators (On Demand Oral) -  Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_4120;    
    This small molecule disrupts capsid functions and it is suitable to long-acting therapy due to its superb antiviral potency, low in vivo clearance and slow drug release kinetics. This talk will highlight some of the structure-based modeling and crystallography efforts that went into our HIV capsid inhibitor discovery program, helping to optimize the antiviral activities and to understand the MOA.
  • ||||||||||  [VIRTUAL] Engineering peptide insertions in virus-like particles using systematic apparent fitness landscapes (On Demand Oral) -  Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_2688;    
    This library generates a discrete map of three amino acid insertions permitted at this location, validates the FG loop as a valuable position for peptide insertion, and illuminates how properties such as charge, flexibility, and hydrogen bonding can interact to preserve or disrupt capsid assembly. Taken together, the results highlight the potential to engineer the MS2 VLP in systematic manner, paving the way to exploring the applications of peptide insertions in biomedically relevant settings.
  • ||||||||||  [VIRTUAL] Development of EVA71 anti-viral compounds (On Demand Oral) -  Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_2403;    
    Future work will involve identifying escape mutants using the “hit” compounds at sub-inhibitory concentrations to identify the potential binding pocket. Further, structure activity relationship studies will be carried out using analogs of the 2 compounds to develop a lead compound which will then be tested in animal models.
  • ||||||||||  GS CA1 / Gilead
    [VIRTUAL] Targeting HIV capsid assembly by long-acting small molecule modulators (Broadcast) -  Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_635;    
    This small molecule disrupts capsid functions and it is suitable to long-acting therapy due to its superb antiviral potency, low in vivo clearance and slow drug release kinetics. This talk will highlight some of the structure-based modeling and crystallography efforts that went into our HIV capsid inhibitor discovery program, helping to optimize the antiviral activities and to understand the MOA.
  • ||||||||||  Review, Journal:  Towards improvements in foot-and-mouth disease vaccine performance. (Pubmed Central) -  Aug 19, 2020   
    However, no alternative vaccines are yet available commercially. Improved disease control globally is clearly beneficial to all countries as it reduces the risk of virus incursions into disease free areas.
  • ||||||||||  Review, Journal:  Nucleocapsid Assembly of Baculoviruses. (Pubmed Central) -  Aug 14, 2020   
    This paper reviews the replication and recombination of baculovirus DNA, expression and transport of capsid proteins, formation of preformed capsids, DNA encapsulation, and nucleocapsid formation. This review will provide a basis for further study of the nucleocapsid assembly mechanism of baculovirus.
  • ||||||||||  Journal:  Structural morphing in a symmetry-mismatched viral vertex. (Pubmed Central) -  Jul 30, 2020   
    Remarkably, the local structure of portal morphs to compensate for symmetry-mismatch, forming similar interactions in different capsid environments while maintaining strict symmetry in the rest of the structure. This creates a unique and unusually dynamic symmetry-mismatched vertex that is central to building an infectious virion.
  • ||||||||||  Journal:  BAY 41-4109-mediated aggregation of assembled and misassembled HBV capsids in cells revealed by electron microscopy. (Pubmed Central) -  Jul 8, 2020   
    These two techniques also revealed that the HBc aggregates were accumulations of capsid-like shells with an electron-dense material consisting of HBV core fragments. These findings, shedding light on the ultrastructural organization of HBc aggregates, provide insight into the mechanisms of action of BAY 41-4109 against HBV and will serve as a basis for comparison with other HBV capsid assembly inhibitors.
  • ||||||||||  Journal:  Pyrimidotriazine derivatives as selective inhibitors of HBV capsid assembly. (Pubmed Central) -  Jul 2, 2020   
    Studies on its mechanism of action revealed that the compound interfered with HBV capsid assembly determined by a cell-free capsid assembly system. Thus, the pyrimidotriazine derivatives are considered to be potential leads for novel HBV capsid assembly inhibitors.
  • ||||||||||  Journal:  Competition between Normative and Drug-Induced Virus Self-Assembly Observed with Single-Particle Methods. (Pubmed Central) -  Jun 26, 2020   
    The smallest particles were T = 4 icosahedra, whereas the larger particles were defective spheres, ellipsoids, and bacilliform cylinders, with regions of T = 4 geometry interspersed with flat regions. Deviation from the spherical T = 4 geometry progressively increased with particle size, which is consistent with the interpretation of a competition between two alternative assembly pathways.
  • ||||||||||  Review, Journal:  The amazing HK97 fold: versatile results of modest differences. (Pubmed Central) -  Jun 8, 2020   
    The procapsid is a metastable state that increases in stability as a result of morphological changes that occur during the dsDNA packaging reaction. We review evidence from several systems indicating that proper contacts acquired in the assembly of the procapsid are critical to forming the correct morphology in the mature capsid.
  • ||||||||||  Review, Journal:  Mass spectrometry-based studies of virus assembly. (Pubmed Central) -  Jun 8, 2020   
    Recent highlights in this field in terms of MDa mass measurements, identification of capsid intermediates, and the effect of external parameters on assembly are discussed. Examples from ion mobility spectrometry-mass spectrometry, charge detection mass spectrometry, and gas-phase electrophoretic molecular analysis research are presented.
  • ||||||||||  Review, Journal:  Virus capsid assembly across different length scales inspire the development of virus-based biomaterials. (Pubmed Central) -  Jun 8, 2020   
    This has inspired scientists to design and construct virus capsid-based functional nano-materials. This review provides some insight into the assembly of virus capsids across several length scales, and certain properties that arise at different levels, providing examples found in naturally occurring systems and those that are synthetically designed.
  • ||||||||||  Journal, Oncolytic Virus, IO Biomarker:  Antiangiogenic VEGF-Blocking Peptides Displayed on the Capsid of an Infectious Oncolytic Parvovirus: Assembly and Immune Interactions. (Pubmed Central) -  Jun 4, 2020   
    Significantly, chimeric MVM-VEbp was able to evolve resolving the structural restrictions by selecting mutations within the engineered peptides that restored efficient capsid assembly. This data shows the promise of anti-neovascularization vaccines using chimeric VEbp-icosahedral capsids of oncolytic viruses, but also raises safety concerns regarding the genetic stability of manipulated infectious parvoviruses in cancer and gene therapies.
  • ||||||||||  Vemlidy (tenofovir alafenamide) / Gilead
    [VIRTUAL] Novel cell culture 3D model for HBV/HIV co-infection and antiviral evaluation (Poster Area) -  May 30, 2020 - Abstract #EASLILCI2020EASL-ILC-I-1844;    
    This novel model was reproducible and provided multiple and simultaneous modalities to quantify HIV-1 and HBV replication; this system can be used to measure key cellular events that drive pathogenesis of HIV-1/HBV in co-infected individuals, and can also be used to identify novel agents that block these events in the context of a relevant cellular system of co-infection. More importantly, we validated this novel organoid system of co-infection as a model for HBV infection and antiviral evaluation.
  • ||||||||||  AB-506 / Arbutus
    [VIRTUAL] Hepatitis B virus core protein variants observed in a first-in-human placebo-controlled study of a core protein inhibitor (Poster Area) -  May 30, 2020 - Abstract #EASLILCI2020EASL-ILC-I-1760;    
    HBV DNA extraction was performed on plasma collected from the 24 non-cirrhotic, HBeAg- positive or -negative, HBV DNA-positive subjects enrolled in AB-506-001 (randomized 10:2 per cohort to AB-506 versus placebo) and 28 subjects that were screened but not enrolled in the study... These findings highlight the importance of conducting molecular epidemiology studies to assess the prevalence of circulating CI-resistant variants as well as developing next-generation CIs with improved coverage of these variants.
  • ||||||||||  Journal:  Phosphorylation of HPV-16 L2 Contributes To Efficient Virus Infectious Entry. (Pubmed Central) -  May 29, 2020   
    We show that this modification plays an essential role in infectious entry, where it modulates susceptibility of the incoming virus to capsid disassembly. These studies therefore define a completely new means of regulating the Papillomavirus L2 proteins; a regulation that optimizes endocytic processing and subsequent completion of the infectious entry pathway.
  • ||||||||||  Review, Journal:  Targets and future direct-acting antiviral approaches to achieve hepatitis B virus cure. (Pubmed Central) -  May 28, 2020   
    New direct-acting antivirals for HBV in development include entry inhibitors, capsid assembly modulators, and drugs targeting cccDNA or HBV RNA, and HBsAg secretion inhibitors. In this Review, we discuss potential targets and direct-acting antiviral approaches in development.
  • ||||||||||  Journal:  Capsid Structure of a Freshwater Cyanophage Siphoviridae Mic1. (Pubmed Central) -  May 23, 2020   
    The novel-fold cement protein gp47 sticks at the two-fold symmetric axis and further fixes the capsid. These findings provide structural insights into the assembly of cyanophages, and set up a platform to explore the mechanism of specific interactions and co-evolution with cyanobacteria.
  • ||||||||||  Journal:  Dynamics of Zika virus capsid protein in solution: properties and exposure of the hydrophobic cleft are controlled by the α-helix 1 sequence. (Pubmed Central) -  May 15, 2020   
    Based on the findings described here, we propose that the dynamics of ZIKVC structural elements responds for a structure-driven regulation of protein interaction with intracellular hydrophobic interfaces, which would impact in the switches necessary for nucleocapsid assembly. Subtle differences in the sequence of α-helix 1 impact on its size and orientation and on the degree of exposure of the hydrophobic cleft, suggesting that α-helix 1 is a hotspot for evolutionary adaptation of flaviviruses' capsid proteins.
  • ||||||||||  Journal:  Discovery of novel hepatitis B virus nucleocapsid assembly inhibitors. (Pubmed Central) -  Apr 24, 2020   
    Drug resistant profile analyses indicated that BA-53038B most likely bound to the HAP pocket, but obviously modulated HBV capsid assembly in a distinct manner. BA-53038B and other CpAMs reported herein provide novel structure scaffolds for the development of core protein-targeted antiviral agents for the treatment of chronic hepatitis B.
  • ||||||||||  Journal:  Evolution of Intermediates during Capsid Assembly of Hepatitis B Virus with Phenylpropenamide-based Antivirals. (Pubmed Central) -  Apr 24, 2020   
    Dilution of the reaction solutions led to the rearrangement of the incomplete particles and demonstrated that these large intermediates may be on-path, but are labile, and exist in a frustrated dynamic equilibrium. During capsid assembly, phenylpropenamide molecules modestly increase the association energy of dimers, prevent intermediates from dissociating, and lead to kinetic trapping where the formation of too many capsids has been initiated leading to both empty and incomplete particles.
  • ||||||||||  Preclinical, Journal:  Discovery of New Hepatitis B Virus Capsid Assembly Modulators by an Optimal High-throughput Cell-based Assay. (Pubmed Central) -  Apr 24, 2020   
    Further studies revealed that 1 and 2 reduced extracellular HBV DNA, HBeAg and intracellular HBV intermediates, including total DNA, RNA and precore RNA of HBV. Size exclusion chromatography (SEC) and electron microscopy (EM) investigations demonstrated that 1 and 2 remarkably induce the formation of morphologically intact capsids and accelerate the dynamics of capsid assembly，suggesting that both 1 and 2 were type I capsid assembly modulators (CAMs).
  • ||||||||||  lamivudine / Generic mfg.
    Journal:  Naturally occurring core protein mutations compensate for the reduced replication fitness of a lamivudine-resistant HBV isolate. (Pubmed Central) -  Apr 10, 2020   
    However, the LMV-resistant virus harboring compensatory core mutations remains sensitive to capsid assembly modulators (CpAMs). Taken together, our study suggests that the enhanced HBV nucleocapsid formation resulting from core mutations represents an important viral strategy to surmount the antiviral drug pressure and contribute to viral pathogenesis, and CpAMs hold promise for developing the combinational antiviral therapy for hepatitis B.