Capsid assembly mod 
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  • ||||||||||  Journal:  Discovery of Phthalazinone Derivatives as Novel Hepatitis B Virus Capsid Inhibitors. (Pubmed Central) -  Nov 26, 2020   
    Structure-activity relationship studies based on metabolic pathways of 4r led to the identification of a phthalazinone derivative 19f with appropriate anti-HBV potencies (IC = 0.014 ± 0.004 μM in vitro), which demonstrated high oral bioavailability and liver exposure. In the AAV-HBV/mouse model, administration of 19f resulted in a 2.67 log reduction of the HBV DNA viral load during a 4-week treatment with 150 mg/kg dosing twice daily.
  • ||||||||||  Journal:  Atomic-resolution structure of HIV-1 capsid tubes by magic-angle spinning NMR. (Pubmed Central) -  Nov 14, 2020   
    The inherent curvature in the CA tubes is controlled by conformational variability of residues in the linker region and of dimer and trimer interfaces. The present structure reveals atomic-level detail in capsid architecture and provides important guidance for the design of novel capsid inhibitors.
  • ||||||||||  Journal:  Adeno-associated virus capsid protein expression in Escherichia coli and chemically defined capsid assembly. (Pubmed Central) -  Nov 12, 2020   
    VLPs developed without assembly-activating protein (AAP), but adding purified recombinant AAP to the refolding process increased capsid yield. Our findings offer a new route to understand AAV assembly biology and open a toolbox for AAV production strategies that might enable capsid display for vaccination and matching of capsids with cargoes at large scale and low cost.
  • ||||||||||  Review, Journal:  Advances in hepatitis B therapeutics. (Pubmed Central) -  Nov 1, 2020   
    Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss...Drugs in more advanced stages of clinical development are bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV and REP-2139...The current goal is to achieve a 'functional cure', with sustained serum HBsAg after drug discontinuation. Ultimately, the goal of HBV therapy will be virus eradication, an achievement that would require the elimination of the cccDNA reservoir within infected hepatocytes.
  • ||||||||||  Journal:  The carboxyl terminus (CT) of the PCV2 capsid protein (Cap) is critical to VLP assembly, cell entry, and propagation. (Pubmed Central) -  Oct 24, 2020   
    Our findings, therefore, suggest that the CT should be considered as one of the key epitopes, recognized by neutralizing antibodies, for vaccine design and a target for drug development to prevent PCV2-associated diseases (PCVAD). Furthermore, it is important to respect the function of K for its role in cell entry if employing either PCV2 VLPs for nanoscale DNA/drug cell delivery or the use of PCV2 VLPs to display a variety of foreign epitopes for immunization.
  • ||||||||||  Journal:  Role of the C-terminal cysteines in virus-like particle formation and oligomerization of the hepatitis E virus ORF2 truncated proteins. (Pubmed Central) -  Oct 21, 2020   
    Herein, by analyzing a set of ORF2 truncated proteins expressed in Escherichia coli, we found that the highly conserved C-terminal cysteines play a crucial role in the oligomerization of the truncated ORF2 proteins and in their assembly into VLPs, through the formation of dimer-dimer disulfide bonds; and the treatment of native HEV particles with dithiothreitol (DTT) induced the disassembly of the viral capsid, suggesting that the disulfide bonding is required for stabilizing the native HEV capsid. The present study sheds light on the structural role of the C-terminal region of the HEV capsid protein and contributes to the full understating of the viral capsid assembly process.
  • ||||||||||  Journal:  SR/RS Motifs as Critical Determinants of Coronavirus Life Cycle. (Pubmed Central) -  Sep 27, 2020   
    A precise and tight regulation of their function is achieved through phosphorylation of a number of serine residues within the SR/RS motifs by the Serine-Arginine protein kinases (SRPKs) that lead to delicate structural alterations. Given that coronavirus N proteins also contain SR/RS domains, we formulate the hypothesis that the viruses exploit the properties of these motifs to promote unpacking of viral RNA and virion assembly.
  • ||||||||||  Journal:  SAR studies in the sulfonyl carboxamide class of HBV capsid assembly modulators. (Pubmed Central) -  Sep 24, 2020   
    The core protein oligomerizes to form the viral capsid, and modulation of the HBV capsid assembly process has shown clinical efficacy in early clinical trials. Herein is described the SAR exploration of NVR 3-778, the first clinical compound in the sulfonyl carboxamide class.
  • ||||||||||  Journal:  A Multiscale Model for the Self-assembly of Coat Proteins in Bateriophage MS2. (Pubmed Central) -  Sep 21, 2020   
    This is, to the best of our knowledge, the first multiscale model to simulate the assembling process of coat proteins in Bacteriophage MS2. The generality of this approach opens the door to its further applications in assembly of other viral capsids, virus-like particles and novel drug delivery systems.
  • ||||||||||  Review, Journal:  Geometric architecture of viruses. (Pubmed Central) -  Sep 16, 2020   
    Biologically significant defective capsids with or without nucleic acids are common in enveloped alpha-, flavi- and hepadnaviruses. The self-assembling, stable and non-infectious virus-like particles have been widely exploited as vaccine candidates and therapeutic molecules delivery vehicles.
  • ||||||||||  Prevymis (letermovir) / Merck (MSD), acyclovir / Generic mfg.
    Journal:  DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses. (Pubmed Central) -  Sep 11, 2020   
    Acyclovir is the drug of choice for HSV encephalopathy, yet there is an estimated 6-19% mortality rate with half of the survivors experiencing moderate to severe chronic neurological deficits...Drug resistance is a concern for HCMV, HSV, and VZV since approved drugs share common mechanisms of action. Targeting DNA encapsidation or capsid assembly provide additional options for the development of non-nucleoside, small molecule anti-herpesviral drugs.
  • ||||||||||  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.