Capsid assembly mod 
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  • ||||||||||  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:  Kaposi's sarcoma-associated herpesvirus ORF17 plays a key role in capsid maturation. (Pubmed Central) -  Dec 30, 2021   
    Furthermore, wild type KSHV produced a mature capsid, whereas ORF17-deficient and protease-dead KSHV produced a B-capsid, (i.e., a closed body possessing a circular inner structure). Therefore, ORF17 and its protease function are essential for appropriate capsid maturation.
  • ||||||||||  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.
  • ||||||||||  Journal:  Unravelling the involvement of cilevirus p32 protein in the viral transport. (Pubmed Central) -  Nov 17, 2021   
    Furthermore, we report that MP possess the capacity to enter the nucleolus and to bind to a major nucleolar protein, the fibrillarin. Based on our findings, we provide a model for the role of the p32 in the intra- and intercellular viral spread.
  • ||||||||||  Journal:  SNAP47 Interacts with ATG14 to Promote VP1 Conjugation and CVB3 Propagation. (Pubmed Central) -  Nov 17, 2021   
    Finally, we revealed that disulfide interactions had an important role in strengthening VP1 conjugation. Collectively, our study elucidated a mechanism by which SNAP47 and ATG14 promoted CVB3 propagation through facilitating viral capsid assembly.
  • ||||||||||  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.
  • ||||||||||  [VIRTUAL] Revealing the mechanisms of viral capsid assembly using computational approaches (Room: Zoom Room 09) -  Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_7189;    
    Formulas generated for the total number of each binding mode within one capsid show the mode within trisymmetron are dominating the stabilization of the capsid which is consistent to previous observation. Besides the viral capsid assembly, methods introduced in this study can be applied to study more complicated assembly process for other biomolecular structures.
  • ||||||||||  [VIRTUAL] HPV virus-like particle formation conserves key structural elements to ensure assembly across types (Room: Virtual Room) -  Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_3372;    
    These conserved structures play an important role in enabling both capsid assembly as well as drive the formation of inter-capsomere disulfide bonds that provide long-term stability for the capsid. Finally, we analyze Cryo-EM structures of other types and demonstrate high conservation of these important 3D structural motifs across structures, even where sequence conservation is not maintained, suggesting synthetic targets that could promote the high-fidelity assembly of VLPs across types.
  • ||||||||||  Approaches for mining natural products databases for ribonucleocapsid assembly inhibitors (Room: Hall B4) -  Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_2277;    
    In the initial studies, we report that the highest-ranking compounds bind to the RNA binding site of N protein. This approach seems feasible for the identification of lead compounds in the discovery of inhibitors that target a crucial step in the life cycle of zoonotic RNA viruses.
  • ||||||||||  Preclinical, Journal:  Capsid assembly is regulated by amino acid residues asparagine 47 and 48 in the VP2 protein of porcine parvovirus. (Pubmed Central) -  Aug 7, 2021   
    Site-directed mutation at 48Asn did not affect the ability of monomers to form into oligomers, but destroyed the ability of oligomers to assemble into macromolecular particles, influencing both capsid assembly and HA activity. Our findings provide valuable information on the mechanisms of PPV capsid assembly and the possibility of chimeric VLP vaccine development by replacing the first 47 amino acids at the N-terminal of the VP2 protein.
  • ||||||||||  Journal:  Dynamics of the SARS-CoV-2 nucleoprotein N-terminal domain triggers RNA duplex destabilization. (Pubmed Central) -  Jul 28, 2021   
    Based on experimental information available in the literature, we constructed kinetics models for N-NTD-mediated dsRNA melting. Our results support a 1:1 stoichiometry (N-NTD:dsRNA), matching MD simulations and raising different possibilities for N-NTD action: (i) two N-NTD arms of dimeric N would bind to two different RNA sites, either closely or spatially spaced in the viral genome, in a cooperative manner; (ii) monomeric N-NTD would be active, opening up the possibility of a regulatory dissociation event.
  • ||||||||||  Journal:  Asymmetric reconstruction of mammalian reovirus reveals interactions among RNA, transcriptional factor µ2 and capsid proteins. (Pubmed Central) -  Jul 23, 2021   
    Polymerase complexes in three Spinoreovirinae subfamily members are organized with different pseudo-D symmetries to engage their highly diversified genomes. The above interactions and those between symmetry-mismatched receptor-binding σ1 trimers and RNA-capping λ2 pentamers balance competing needs of capsid assembly, external protein removal, and allosteric triggering of endogenous RNA transcription, before, during and after infection, respectively.