Capsid assembly mod 
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  • ||||||||||  Journal:  HBV polymerase recruits the phosphatase PP1 to dephosphorylate HBc-Ser170 to complete encapsidation. (Pubmed Central) -  Feb 11, 2025   
    Therefore, HBV Pol may play a dual role by initially bringing pgRNA to phosphorylated HBc and recruiting PP1 for later completion of RNA packaging into the capsids. These findings not only decipher the mechanism by which Pol-mediated dephosphorylation of HBc regulates pgRNA encapsulation, but also reveal the possibility of PP1 as a potential target for antiviral development.
  • ||||||||||  Journal:  Local Microenvironments of capsomer variants in the PBCV-1. (Pubmed Central) -  Feb 3, 2025   
    Moreover, the identified salt bridges between Type V/I capsomers and their surrounding capsomers corroborate the results of electrostatic calculations, further highlighting the important residues involved in these interactions. Understanding these local capsid microenvironments will be essential to elucidate the mechanisms governing viral capsid assembly.
  • ||||||||||  Sunlenca (lenacapavir) / Gilead
    Journal:  The primary mechanism for highly potent inhibition of HIV-1 maturation by lenacapavir. (Pubmed Central) -  Jan 27, 2025   
    Consequently, LEN treatment results in morphologically atypical virus particles containing malformed, hyper-stable CA assemblies, which fail to infect target cells. Moreover, we have uncovered an inverse correlation between inhibitor potency and CA levels in cell culture assays, which accounts for LEN's ability to potently (with picomolar EC50 values) inhibit HIV-1 maturation at clinically relevant drug concentrations.
  • ||||||||||  Journal:  Rabies virus phosphoprotein exhibits thermoresponsive phase separation with a lower critical solution temperature. (Pubmed Central) -  Jan 12, 2025   
    Protein dimers assemble already below the saturation concentration, and condensation is driven by attractive conformation-specific interactions leading to reentrant liquid phase separation over a narrow range of salt concentration. We propose a minimal molecular model in which P can adopt three limit conformational states and the disordered N-terminal arms control the interactions between giant dipoles that is consistent with our observations.
  • ||||||||||  Journal:  Research Status and Applications of Adeno-Associated Virus. (Pubmed Central) -  Dec 26, 2024   
    Additionally, it examines the utilization of recombinant adeno-associated viruses (rAAV), detailing their production methods, mechanisms of cell entry and trafficking, and various serotypes. The review further interprets the role of rAAV by analyzing its current applications in research and therapy.
  • ||||||||||  Sunlenca (lenacapavir) / Gilead
    Journal:  The primary mechanism for highly potent inhibition of HIV-1 maturation by lenacapavir. (Pubmed Central) -  Dec 16, 2024   
    Our studies here have elucidated previously undescribed structural and mechanistic bases for a highly potent antiviral activity of LEN during viral egress. These findings will inform clinical applications of LEN as a potent HIV-1 maturation inhibitor and aid the development of second-generation inhibitors targeting assembly of the mature viral capsid.
  • ||||||||||  morphothiadine mesilate (GLS4) / HEC Pharm
    Journal:  Identification of peptide-based hepatitis B virus capsid inhibitors based on the viral core protein. (Pubmed Central) -  Dec 7, 2024   
    Molecular dynamics simulations revealed that despite their overlapping sequence, 19Ac and 20Ac bonded to different regions of the core protein, thereby inhibiting capsid assembly through distinct mechanisms. These peptides could serve as valuable seed compounds for the further development of HBV capsid inhibitors, including GLS4-resistant strains.
  • ||||||||||  Journal:  Cryo-EM structure of single-layered nucleoprotein-RNA complex from Marburg virus. (Pubmed Central) -  Nov 28, 2024   
    We determined by cryogenic electron microscopy (cryo-EM) the MARV helical ribonucleoprotein (RNP) complex structure in single-layered conformation, which differs from the previously reported structure of a double-layered helix. Our findings illuminate novel RNP interactions and expand knowledge on MARV genome packaging and nucleocapsid assembly, both processes representing attractive targets for the development of antiviral therapeutics against MARV disease.
  • ||||||||||  ALG-000184 / Aligos Therap
    Preclinical, Journal:  The Discovery and Preclinical Profile of ALG-000184, a Prodrug of the Potent Hepatitis B Virus Capsid Assembly Modulator ALG-001075. (Pubmed Central) -  Nov 22, 2024   
    ALG-001075 was further advanced through clinical development as the highly soluble prodrug ALG-000184. ALG-000184 is currently being explored in multiple clinical trials in HBV-infected subjects where unprecedented reductions in HBV DNA, RNA and other viral antigens have been observed, making ALG-000184 a promising candidate to become a cornerstone for future chronic suppressive and combination treatment regimens for CHB.
  • ||||||||||  Journal:  The conserved cysteines at position 18, 36, and 49 of Autographa californica multiple nucleopolyhedrovirus VP39 are essential for virus replication. (Pubmed Central) -  Nov 16, 2024   
    Immunofluorescence analysis by confocal microscopy revealed that the subcellular localization of VP39 with mutations in Cys18, Cys36 or Cys49 was exclusively distributed in the cytoplasm of a cell regardless of virus infection or not, while the wild-type VP39 or the VP39 carrying mutations in Cys29, Cys132, Cys169, Cys229, or Cys232 was distributed throughout the cytoplasm and the nucleus. Our results demonstrated that Cys18, Cys36, and Cys49 are essential for the proper localization of VP39, which is a prerequisite for successful nucleocapsid assembly of the virus.
  • ||||||||||  Preclinical, Journal:  Long-term 3D cell culture models for hepatitis B virus studies. (Pubmed Central) -  Nov 13, 2024   
    As a proof-of-concept we used our de novo HBV-infected model as a drug-testing platform to validate an HBV capsid assembly modulator (CpAM). We report that we have established two HBV-infected 3D cell culture models and have characterized these models as practical and novel approaches with the potential to enhance the relevance and scope of in vitro HBV studies.
  • ||||||||||  AB-836 / Arbutus
    Preclinical, Journal:  Preclinical and Clinical Antiviral Characterization of AB-836, a Potent Capsid Assembly Modulator Against Hepatitis B Virus. (Pubmed Central) -  Nov 13, 2024   
    Furthermore, HBV DNA sequence analysis of baseline samples from the Phase 1 study revealed that 51.4% of the chronic hepatitis B participants contained at least one core polymorphism within the CAM-binding pocket, suggesting that genetic variations exist at this site. While AB-836 was discontinued due to clinical safety findings, data from the preclinical and clinical studies could help inform future optimization of HBV CAMs.
  • ||||||||||  Review, Journal:  Novel mechanistic insights - A brand new Era for anti-HBV drugs. (Pubmed Central) -  Oct 27, 2024   
    The development of cccDNA reducers is particularly critical, as they directly target the persistent viral reservoir, offering a promising pathway towards achieving a functional cure or complete viral eradication. Continued research in this area is essential to advance the effectiveness of anti-HBV therapies.
  • ||||||||||  imdusiran (AB-729) / Arbutus
    Journal:  Control of Hepatitis B Virus with Imdusiran, a Small Interfering RNA Therapeutic. (Pubmed Central) -  Oct 11, 2024   
    Imdusiran did not intrinsically stimulate cytokine release in healthy donor human whole blood, supportive of its mechanism of action as a direct acting RNA interference antiviral. Taken together, these data support imdusiran in combination treatment approaches toward chronic hepatitis B functional cure.
  • ||||||||||  Investigating the Antiphage Defense Systems in Staphylococcal Phage Satellite (Convention Center - Hall I-1 (1st Floor); In-Person-Only) -  Oct 11, 2024 - Abstract #ASTMH2024ASTMH_1536;    
    The interference mechanism by SaPIpT1028 is dependent on a new SaPI-encoded gene, rcp (redirecting capsid packaging), encoding a protein involved in remodelling the phage capsid into a small capsid to package the SaPI genome. This study has also identified a novel interference strategy involving an accessory gene, sma (single-protein MazF-like antiphage system), encoded at the 5' region of the island genome, that offers protection to its recipient host and the SaPI-inducing phages from other phage infection, shedding light on PICI evolution and the mutual relationship between PICIs and their helper phages.
  • ||||||||||  Journal:  CAM-A-dependent HBV core aggregation induces apoptosis through ANXA1. (Pubmed Central) -  Oct 10, 2024   
    The study demonstrated that a CAM subtype, CAM-A-induced formation of aberrant structures from HBV core protein aggregates in the nucleus leading to cell death by ANXA1-driven apoptosis. Thus, CAM-A treatment may lead to the specific elimination of HBV-infected cells by apoptosis, paving the way to novel therapeutic strategies for viral cure.
  • ||||||||||  Review, Journal:  Strategies for developing phages into novel antimicrobial tailocins. (Pubmed Central) -  Oct 2, 2024   
    This article reviews three strategies for producing tailocins: disrupting the capsid-tail junction of phage particles, blocking capsid assembly during phage propagation, and creating headless phage particles synthetically. Particularly appealing is the production of tailocins through synthetic biology using phages with contractile tails as scaffolds to unlock the antimicrobial potential of tailocins.
  • ||||||||||  Journal:  Conformationally Constrained Isoquinolinones as Orally Efficacious Hepatitis B Capsid Assembly Modulators. (Pubmed Central) -  Sep 20, 2024   
    Key analogues demonstrated single digit nM EC50 values in reducing HBV DNA in a HepDE19 cellular assay in addition to favorable ADME and pharmacokinetic properties, leading to a high degree of oral efficacy in a relevant in vivo hydrodynamic injection mouse model of HBV infection, with 12e effecting a 3 log10 decline in serum HBV DNA levels at a once daily dose of 1 mg/kg. Additionally, maintenance of activity was observed in clinically relevant HBV core protein variants T33N and I105T.
  • ||||||||||  Journal:  Phosphatidylinositol-3-phosphate mediates Arc capsid secretion through the multivesicular body pathway. (Pubmed Central) -  Aug 23, 2024   
    These results suggest that unlike the HIV Gag, whose membrane targeting requires interaction with plasma-membrane-specific phosphatidyl inositol (4,5) bisphosphate (PI(4,5)P2), the assembly of Arc capsids is mediated by PI3P at endocytic membranes. Understanding Arc's secretion pathway helps gain insights into its role in intercellular cargo transfer and highlights the commonality and distinction of trafficking mechanisms between structurally resembled capsid proteins.
  • ||||||||||  Journal:  Arg18 Substitutions Reveal the Capacity of the HIV-1 Capsid Protein for Non-Fullerene Assembly. (Pubmed Central) -  Jul 31, 2024   
    The Arg18 mutant pentamers resemble the hexamer in intra-oligomeric contacts and form a unique tetramer-of-pentamers that allows for incorporation of an octahedral vertex with a cross-shaped opening in the hexagonal capsid lattice. Our findings highlight an unexpected degree of structural plasticity in HIV-1 capsid assembly.
  • ||||||||||  vebicorvir (ABI-H0731) / Assembly Biosci
    Journal:  A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B. (Pubmed Central) -  Jul 29, 2024   
    By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug's dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection...We developed a multiscale model of the intracellular HBV lifecycle and extracellular dynamics using a time-since-infection structured partial differential equation. We fit the model to participant data from a recent phase I trial, performed a detailed parameter sensitivity analysis, identified key mechanisms driving viral response to first-generation CAM treatment, and demonstrated that HBV RNA is more sensitive than HBV DNA to changes in CAM efficacy, highlighting the potential role of HBV RNA as a biomarker for CAM effectiveness.
  • ||||||||||  Journal:  Exploring the Effects of Intersubunit Interface Mutations on Virus-Like Particle Structure and Stability. (Pubmed Central) -  Jul 22, 2024   
    Molecular dynamics experiments recapitulated the structural rationale in silico for the single point mutation [S37P] forming a T = 1 virus-like particle and showed that this assembly state was not favored when combined with mutations that favor rod-like architectures. Through this work, we investigated how interdimer interface dynamics influence VLP size and morphology and how these properties affect particle function in applications such as drug delivery.