- |||||||||| Journal: The Ebola Virus Interferon Antagonist VP24 Undergoes Active Nucleocytoplasmic Trafficking. (Pubmed Central) - Jan 29, 2022
Molecular mapping indicates that cytoplasmic localization of VP24 depends on a CRM1-dependent nuclear export sequence at the VP24 C-terminus. Nuclear export is not required for STAT1 antagonism, consistent with competitive karyopherin binding being the principal antagonistic mechanism, while export mediates return of nuclear VP24 to the cytoplasm where replication/nucleocapsid assembly occurs.
- |||||||||| Using computational approach to reveal the mechanisms of viral capsid assembly (Room 25B (San Diego Convention Center)) - Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_12706;
This explains why the seam between two neighboring trisymmetrons becomes the breaking line when a giant virus capsid dissociates. Besides the viral capsid assembly, methods introduced in this study can be applied to study more complicated assembly process for other biomolecular structures.Structures of Paramecium Bursaria Chlorella Virus 1 (PBCV-1) capsid and its capsomers.
- |||||||||| Journal: Oxadiazepinone HBV Capsid Assembly Modulators. (Pubmed Central) - Jan 8, 2022
Modulation of the HBV capsid assembly has shown efficacy in early clinical trials through use of small molecule capsid assembly modulators (CAMs). Herein is described the evolution and SAR of a novel pyrazolo piperidine lead series into advanced oxadiazepinone HBV CAMs.
- |||||||||| Preclinical, Journal: In vitro assembly and evaluation of Nora virus VLPs. (Pubmed Central) - Jan 6, 2022
Assemblies that contained VP4A and/or VP3 created VLPs with similar sizes to purified empty Nora virus capsids, potentially indicating that VP4A and/or VP3 are vital for Nora virus capsid structure, assembly, and/or stability. Not only does this study provide insight into the role of Nora virus proteins, but it may also lead to a deeper understanding of how Nora virus or other picorna-like viruses undergo assembly. Keywords: RNA viruses, Nora virus, picorna-like virus, virus-like particles, capsid assembly.
- |||||||||| Journal: The KSHV ORF20 Protein Interacts with the Viral Processivity Factor ORF59 and Promotes Viral Reactivation. (Pubmed Central) - Jan 1, 2022
We investigated the role of the poorly characterized viral protein ORF20, and through proximity labeling, we found that ORF20 interacts with ORF59 in replication compartments and affects DNA replication and subsequent steps of the late viral life cycle. Collectively, these results provide insights into the possible contribution of ORF20 to the complex lytic DNA replication process and suggest that this highly conserved protein may be an important modulator of this key viral mechanism.
- |||||||||| Journal: Shape shifter: redirection of prolate phage capsid assembly by staphylococcal pathogenicity islands. (Pubmed Central) - Dec 29, 2021
We built atomic models for CP and Ccm, and show that Ccm occupies the pentameric capsomers in the isometric SaPIbov5 procapsids, suggesting that preferential incorporation of Ccm pentamers prevents the cylindrical midsection from forming. Our results highlight that pirate elements have evolved diverse mechanisms to suppress phage multiplication, including the acquisition of phage capsid protein homologs.
- |||||||||| Review, Journal: Novel Therapies of Hepatitis B and D. (Pubmed Central) - Dec 27, 2021
Many of these new promising compounds such as entry inhibitors, covalently closed circular DNA (cccDNA) inhibitors, small interfering RNAs (siRNAs), capsid assembly modulators and nucleic acid polymers are in various stages of clinical developments. In this review article, we provided a comprehensive overview of the structure and lifecycle of HBV, the limitations of the current therapies and a summary of the novel therapeutic agents for both HDV and HBV infection.
- |||||||||| Preclinical, Journal: A novel method for the in vitro assembly of virus-like particles and multimeric proteins. (Pubmed Central) - Dec 16, 2021
Our results pave the way to better understand the role of pORF19 in capsid assembly and identify a potential novel drug target for the treatment of herpesvirus-induced diseases. The novel method presented here is simpler and faster than other reported methods for the assembly and disassembly of viral proteins, a step needed for most applications.
- |||||||||| Vemlidy (tenofovir alafenamide) / Gilead
Journal: Generation of an HBV Core Phenotyping Assay for Evaluating HBV Capsid Compounds. (Pubmed Central) - Nov 29, 2021 Overall, 11 of 13 constructs replicated in vitro, 6 constructs showed reduced susceptibility to CAMs. The 11 polymorphs which could replicate in vitro remained sensitive to the nucleotide analog tenofovir alafenamide (TAF), indicating that there is no cross-resistance.
- |||||||||| Clinical, Journal: Crystal and solution structures reveal oligomerization of individual capsid homology domains of Drosophila Arc. (Pubmed Central) - Oct 27, 2021
This domain-swapped structure resembles the dimeric protein C of flavivirus capsids, as well as the structure of histones dimers, domain-swapped transcription factors, and membrane-interacting BAK domains. The strong oligomerization properties of the isolated dArc lobe domains explain the ability of dArc to form capsids in the absence of any large N-terminal domain, in contrast to the mammalian protein.
- |||||||||| Journal: Recombinant Turnip Yellow Mosaic Virus Coat Protein as a Potential Nanocarrier. (Pubmed Central) - Oct 20, 2021
The C-terminal tail which is exposed on the surface can be exploited as a useful site to display multiple copies of functional ligands. The ability of the chimeric VLPs to self-assemble after undergo chemical denaturation indicates its potential role to serve as a nanocarrier for use in targeted drug delivery.
- |||||||||| Journal: Atomic Structure of the Trichomonas vaginalis Double-Stranded RNA Virus 2. (Pubmed Central) - Oct 13, 2021
Our results reveal the intersubunit interactions driving CSP association for capsid assembly and the properties that govern organization and maintenance of the viral genome. Structural comparison between TVV2 capsids and those of distantly related dsRNA viruses indicates conserved strategies of nascent RNA release and a putative viral guanylyltransferase domain implicated in the cytoplasmic maintenance of viral messenger and genomic RNA.
- |||||||||| BI2536 / Boehringer Ingelheim
Journal: Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes. (Pubmed Central) - Oct 8, 2021 Structural comparison between TVV2 capsids and those of distantly related dsRNA viruses indicates conserved strategies of nascent RNA release and a putative viral guanylyltransferase domain implicated in the cytoplasmic maintenance of viral messenger and genomic RNA. This study emphasizes that a specific PLK1 inhibition could help achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies.
- |||||||||| Journal: RNA Binding Properties of the Ty1 LTR-Retrotransposon Gag Protein. (Pubmed Central) - Sep 17, 2021
We also uncover a relationship between Ty1 RNA structure and Gag binding involving the pseudoknot present on Ty1 gRNA. In all likelihood, the differences in Gag binding affinity detected in vitro only partially explain selective Ty1 RNA packaging into VLPs in vivo.
- |||||||||| Journal: Curvature of the Retroviral Capsid Assembly Is Modulated by a Molecular Switch. (Pubmed Central) - Sep 9, 2021
These residues undergo large torsion angle changes, resulting in a 34° rotation of the C-terminal domain relative to its N-terminal domain around the flexible interdomain linker, without substantial changes of either the conformation of individual domains or the assembly contact interfaces. This knowledge provides new insights to help decipher the mechanism of the retroviral capsid assembly.
- |||||||||| Journal: Identification of a new class of HBV capsid assembly modulator. (Pubmed Central) - Sep 3, 2021
The core protein oligomerizes to form the viral capsid, and modulation of the HBV capsid assembly has shown efficacy in clinical trials. Herein is described the identification and hit to lead SAR of a novel series of pyrazolo piperidine HBV capsid assembly modulators.
- |||||||||| RG7907 / Roche
Journal: What drives the dynamics of HBV RNA during treatment? (Pubmed Central) - Sep 2, 2021 This makes promising the use of core protein allosteric modulators, such as RG7907, which disrupt the nucleocapsid assembly and profoundly reduce HBV RNA...We compare the predictions with those obtained in patients treated with the nucleotide analog tenofovir...The model brings a conceptual framework for understanding the differences between HBV DNA and HBV RNA dynamics. Integration of HBV RNA in viral dynamic models may be helpful to better quantify the treatment effect, especially in viral suppressed patients where HBV DNA is no longer detectable.
|