Capsid assembly mod 
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  • ||||||||||  Journal:  Structures of Hepatitis B Virus Core- and e-Antigen Immune Complexes Suggest Multi-point Inhibition. (Pubmed Central) -  Sep 20, 2019   
    Here, by means of X-ray crystallography, analytical ultracentrifugation, and electron microscopy, we demonstrate that the antibodies have non-overlapping epitopes and effectively block biologically important assemblies of both proteins. These properties, together with the anticipated high tolerability and long half-lives of the antibodies, make them promising therapeutics.
  • ||||||||||  Review, Journal:  Packaging of Genomic RNA in Positive-Sense Single-Stranded RNA Viruses: A Complex Story. (Pubmed Central) -  Sep 20, 2019   
    In vitro and in vivo data show that there are different packaging mechanisms that control selective packaging of the genomic RNA during nucleocapsid assembly. The goals of this article are to explain some of the key experiments that support the contribution of these factors to packaging selectivity and to draw a general scenario that could help us move towards a better understanding of this step of the viral infectious cycle.
  • ||||||||||  Preclinical, Journal:  Hepatitis B virus DNA integration occurs early in the viral life cycle in aninfection model via NTCP-dependent uptake of enveloped virus particles. (Pubmed Central) -  Sep 11, 2019   
    ...HBV DNA integration was efficiently blocked by treatment with a 200 nM concentration of the HBV entry inhibitor Myrcludex B, but not with 10 μM tenofovir, 100 U of interferon alpha, or a 1 μM concentration of the capsid assembly inhibitor GLS4...Using this model, we show that integration already occurs when the infection is first established. Importantly, we provide here a system to analyze molecular factors involved in HBV integration, which can be used to develop strategies to halt its formation.
  • ||||||||||  Journal:  Dynamin is required for efficient cytomegalovirus maturation and envelopment. (Pubmed Central) -  Sep 1, 2019   
    Here we show that dynamin, which is an integral part of host endocytic machinery, is largely dispensable for early stages of CMV infection but is required at a late stage of CMV maturation. Studies on dynamin function in CMV infection will help us understand the host-virus interaction pathways amenable to targeting by conventional small molecules as well as by newer generation nucleotide-based therapeutics (e.g. siRNA, CRISPR/CAS gRNA, etc.).
  • ||||||||||  Journal:  Combining Cell-Free Protein Synthesis and NMR Into a Tool to Study Capsid Assembly Modulation. (Pubmed Central) -  Aug 24, 2019   
    We demonstrate that assembled capsids can be synthesized in amounts sufficient for structural studies, and show that addition of assembly modulators to the cell-free reaction produces objects similar to those obtained by addition of the compounds to preformed Cp183 capsids. These results establish the cell-free system as a tool for the study of capsid assembly modulation directly after synthesis by the ribosome, and they open the perspective of assessing the impact of natural or synthetic compounds, or even enzymes that perform post-translational modifications, on capsids structures.
  • ||||||||||  Journal:  A viral scaffolding protein triggers portal ring oligomerization and incorporation during procapsid assembly. (Pubmed Central) -  Jul 4, 2019   
    We report that preformed dodecameric rings of P22 portal protein, as opposed to portal monomers, incorporate into nascent procapsids, with preference for the procapsid portal conformation. Finally, a novel role for P22 scaffolding protein in triggering portal ring formation from portal monomers is elucidated and validated by incorporating de novo assembled portal rings into procapsids.
  • ||||||||||  Loprox gel/cream/shampoo/topical suspension (ciclopirox topical) / Bausch Health
    Preclinical, Journal:  Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly. (Pubmed Central) -  Jun 9, 2019   
    Ciclopirox synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model. Therefore, orally-administered ciclopirox may provide a novel opportunity to combat chronic HBV infection by blocking HBV capsid assembly.
  • ||||||||||  Review, Journal:  Norovirus assembly and stability. (Pubmed Central) -  Jun 7, 2019   
    Gathering information on these differences and common features may deepen our understanding of norovirus emergence and can potentially be used to distinguish variants. However, more systematic studies and standardized approaches are required.
  • ||||||||||  Review, Journal:  A modelling paradigm for RNA virus assembly. (Pubmed Central) -  Jun 7, 2019   
    The model reveals how multiple sequence-structure motifs in the genomic RNA, termed packaging signals, with a shared coat protein recognition motif enable viruses to overcome a viral assembly-equivalent of Levinthal's Paradox in protein folding. The fitness advantages conferred by this mechanism suggest that it should be widespread in viruses, opening up new perspectives on viral evolution and anti-viral therapy.
  • ||||||||||  Journal:  Solid-state [C-N] NMR resonance assignment of hepatitis B virus core protein. (Pubmed Central) -  Jun 4, 2019   
    A secondary chemical shift analysis of the 140 visible residues suggests an overall alpha-helical three-dimensional fold matching that derived for Cp149 from the X-ray crystallography of the capsid, and from solution-state NMR of the Cp149 dimer. Interestingly, however, at three distinct regions the chemical shifts in solution differ significantly between core proteins in the capsid state versus in the dimer state, strongly suggesting the respective residues to be involved in capsid assembly.
  • ||||||||||  Journal:  Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus. (Pubmed Central) -  May 7, 2019   
    The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections.
  • ||||||||||  Journal:  Crystal Structure of the Capsid Protein from Zika Virus. (Pubmed Central) -  Apr 26, 2019   
    Furthermore, the highly positively charged interface, mainly formed by α4 helix, is proposed to be responsible for nucleotide binding. These findings will greatly enhance our understanding of ZIKV C protein, providing information for anti-ZIKV drug design targeting the C protein.
  • ||||||||||  Journal:  Inhibitors of the HIV-1 capsid, a target of opportunity. (Pubmed Central) -  Apr 9, 2019   
    Small molecules that bind to the viral capsid protein can be potent inhibitors of HIV infection. Capsid-targeting drugs are predicted to exhibit high barriers to viral resistance, and ongoing work in this area is contributing to an understanding of the molecular biology of HIV uncoating and maturation.
  • ||||||||||  Journal:  5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors. (Pubmed Central) -  Mar 28, 2019   
    In the end, these medicinal chemistry efforts led to the identification of multiple analogues strongly binding to Cp, potently inhibiting HBV replication in nanomolar range without cytotoxicity, and exhibiting good oral bioavailability (F). Two of our analogues, 19o (EC = 0.11 μM, CC > 100 μM, F = 25%) and 19k (EC = 0.31 μM, CC > 100 μM, F = 46%), displayed overall lead profiles superior to reported CAEs 7-10 used in our studies.
  • ||||||||||  Preclinical, Journal:  Design and synthesis of aminothiazole based Hepatitis B Virus (HBV) capsid inhibitors. (Pubmed Central) -  Mar 28, 2019   
    This compound exerted potent inhibitory effect upon HBV production, either in cell culture or in mice with no obvious acute toxicity. We propose that further development of this compound could lead to novel potent anti-HBV inhibitors that target HBV capsid assembly.