- |||||||||| Review, Journal: Nuclear entry and egress of parvoviruses. (Pubmed Central) - Oct 26, 2022
An alternative pathway for nuclear export has been described using active transport through the NPC mediated by the chromosome region maintenance 1 protein, CRM1, which is enhanced by phosphorylation of the N-terminal domain of VP2. However, other alternative but not yet uncharacterized nuclear export pathways cannot be excluded.
- |||||||||| Journal: Marine viral particles reveal an expansive repertoire of phage-parasitizing mobile elements. (Pubmed Central) - Oct 25, 2022
In total, the data suggest that marine phage satellites have potential to significantly impact the ecology and evolution of bacteria and their viruses throughout the oceans. We predict that any habitat that harbors bacteriophage will also harbor similar phage satellites, making them a ubiquitous feature of most microbiomes on Earth.
- |||||||||| RG7907 / Roche, ALG-005398 / Aligos Therap
NON-HAP CLASS I CAPSID ASSEMBLY MODULATORS HAVE DISTINCT PROFILES AND A DIFFERENTIATED MECHANISM OF ACTION () - Oct 23, 2022 - Abstract #AASLD2022AASLD_704; Their underlying mechanisms of action governing in vivo HBsAg reduction are also clearly differentiated. Since optimized non-HAP CAM1s have suitable ADME / tox profiles, they represent an attractive class of molecules for further development as a part of potential functional cure regimens for CHB, offering a potential advantage over HAPs.
- |||||||||| Lynparza (olaparib) / Merck (MSD), AstraZeneca
OLAPARIB ENHANCES THE ANTI-VIRAL EFFECT OF CRISPR/Cas9 THERAPY TARGETING HBV GENOME VIA NHEJ-MEDIATED DNA REPAIR MACHINERY () - Oct 23, 2022 - Abstract #AASLD2022AASLD_662; Four days after HBV infection, Cas9 expression was induced by doxycycline (DOX) administration...Treatment of entecavir, interferon α, Bay41-4109 (Capsid Assembly Modulator) did not alter the efficacy of CRISPR/Cas9 treatment in HepG2-hNTCP-iCas9 cells... Inhibition of NHEJ-mediated DNA repair machinery with olaparib enhances the efficacy of CRISPR/Cas9 treatment targeting HBV genome.
- |||||||||| Journal: Antiviral activities of Polygonum Perfoliatum L. extract and related phenolic acid constituents against hepatitis B virus. (Pubmed Central) - Oct 18, 2022
Further study showed that the phenolic acids constituents, protocatechuic acid and gallic acid, but not ethyl caffeate, which are reported enriched in the water extract fraction, showed strong anti-HBV activities in inhibiting viral core DNA synthesis, CCC DNA formation and HBeAg production. These results suggested that the Polygonum perfoliatum L. total extract and the related phenolic acids like protocatechuic acid and gallic acid could inhibit HBV replication and also indicated the potential utility of Polygonum perfoliatum L. and related constituents as sources of novel antivirals against HBV.
- |||||||||| Journal: Filovirus helical nucleocapsid structures. (Pubmed Central) - Oct 16, 2022
Mini-abstract Filovirus nucleocapsid is responsible for viral genome transcription and replication. Here, we summarize the helical nucleocapsid structure of Ebola and Marburg viruses, focusing on the nucleoprotein-RNA helix of the nucleocapsid core structure, which has been recently determined by cryo-electron microscopy.
- |||||||||| Irsp53 facilitates Arc capsid assembly and release during long-term potentiation (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_6773;
Using imaging of live neurons, we find that Arc and IRSp53 colocalize and traffic anterograde from soma to dendrites, sometimes followed by loss of signal that may be release events. These results help elucidate the molecular mechanisms that facilitate Arc capsid assembly and release, identifying a potentially new secretory pathway in neurons.
- |||||||||| Journal: Multiscale Modeling of Hepatitis B Virus Capsid Assembly and Its Dimorphism. (Pubmed Central) - Oct 4, 2022
By constructing Markov state models and employing transition path theory, we identify pathways leading to T = 3, T = 4, and other experimentally observed capsid morphologies. The analysis shows that capsid polymorphism is promoted by the low HBV capsid bending modulus, where the key factors controlling polymorphism are the conformational energy landscape and protein-protein binding affinities.
- |||||||||| Hepcludex (bulevirtide) / Gilead
Journal: Cautious optimism in anticipation of hepatitis B curative therapies. (Pubmed Central) - Sep 29, 2022 The new emerging approaches hold promise to achieve cure and loss of hepatitis B surface antigen. Studies or clinical trials investigating new therapies remain small and either focus on patients with low viral load and without hepatotoxic injury or patients with hepatitis D co-infection, which makes it challenging to assess their effectiveness and side effect profile in hepatitis B population.
- |||||||||| Journal: Characterization of a Primordial Major Capsid-Scaffolding Protein Complex in Icosahedral Virus Shell Assembly. (Pubmed Central) - Sep 21, 2022
A model is described wherein dynamic interactions between MCP proteins play an essential role in high fidelity viral shell assembly. Scaffold-chaperoned MCP polymerization is a strongly conserved process in all the large dsDNA viruses and our results provide insight into this primordial complex in solution and have broad biological significance in our understanding of virus assembly mechanisms.
- |||||||||| Journal: Role of VP30 Phosphorylation in Ebola Virus Nucleocapsid Assembly and Transport. (Pubmed Central) - Sep 20, 2022
Our work determines the localization of VP30 at the surface of ruffled nucleocapsids, which differs from the localization of polymerase in EBOV-infected cells. This study sheds light on the novel role of VP30 phosphorylation in nucleocapsid assembly, which is an important prerequisite for virion formation.
- |||||||||| Journal: Design, synthesis and biological evaluation of novel dihydrobenzodioxine derivatives as HBV capsid protein inhibitors. (Pubmed Central) - Sep 14, 2022
Compound 5a (EC = 0.50 ± 0.07 μM, CC = 48.16 ± 9.15 μM) showed better anti-HBV DNA replication activity than the lead compound BA-38017, and showed good inhibitory effect on the assembly of HBV capsid protein compared with the clinical drug NVR 3-778. In addition, preliminary structure-activity relationship (SAR) and molecular docking studies were conducted to explore potential interactions and binding modes between compounds and target proteins, which may help researchers to find more effective anti-HBV drugs.
- |||||||||| Zokinvy (lonafarnib) / Eiger
Review, Journal: Future anti-HDV treatment strategies, including those aimed at HBV functional cure. (Pubmed Central) - Aug 11, 2022 Drugs only active against HDV, such as lonafarnib, have shown efficacy in combination with nucleoside analogues and peginterferon, but do not lead to HBsAg loss...Immunomodulators on their own seldom achieve functional cure, hence these agents in combination to assess the optimal combination are being investigated. Consequently, agents leading to functional cure of HBV are ideal for both HBV and HDV.
- |||||||||| morphothiadine mesilate (GLS4) / HEC Pharm
Computational prediction of susceptibility and resistance for HBV capsid assembly effectors (Hall F2 (McCormick Place Convention Center)) - Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_9079; The results also suggest that GLP-26 will possess broad anti-HBV activity, more so than GLS4. This study demonstrates the utility of computational resistance prediction in the context of drug discovery, which can be applied to many viral protiens.
- |||||||||| Journal: Diazepinone HBV Capsid Assembly Modulators. (Pubmed Central) - Jul 28, 2022
Interfering with capsid assembly has shown efficacy in clinical trials with small molecule capsid assembly modulators (CAMs). Herein is described the further optimization of a progressive series of diazepinone HBV CAMs.
- |||||||||| Journal: The Dynamics of Viruslike Capsid Assembly and Disassembly. (Pubmed Central) - Jul 23, 2022
We explain our experimental findings using a simple model based on classical nucleation theory applied to virus capsids, in which we account for the change in the free protein concentration, as the different types of shells assemble and disassemble by shedding or absorbing single protein subunits. As far as we are aware, this is the first study confirming that both the assembly and disassembly of viruslike shells can be explained through classical nucleation theory, reproducing quantitatively results from time-resolved experiments.
- |||||||||| Journal: Development and Characterization of an Inducible Assay System to Measure Zika Virus Capsid Interaction. (Pubmed Central) - Jul 14, 2022
By using of this system, peptides (Pep.15-24 in the N-terminal region of ZIKV capsid protein and Pep.44-58 in the ?2 helix of ZIKV capsid protein) were identified to inhibit ZIKV capsid-capsid interaction. Overall, this study developed a novel inducible assay system to measure ZIKV capsid interaction and identify ZIKV capsid multimerization inhibitors, which will be applied for future discovery of ZIKV assembly inhibitors.
- |||||||||| Review, Journal, IO biomarker: Getting to HBV cure: the promising paths forward. (Pubmed Central) - Jun 22, 2022
Many obstacles remain, such as overcoming translational failures, choosing the right endpoint using the right biomarkers, and leveraging current treatments in combination regimens to enhance response rates. This review gives an overview of the current therapies for CHB, HBV biomarkers used to evaluate treatment response, and development of DAAs and immune-targeting drugs, and discusses the limitations and unanswered questions on the journey to HBV cure.
- |||||||||| Journal: Insights into the capsid structure of banana bunchy top virus. (Pubmed Central) - Jun 14, 2022
Comparison with the CP and capsid structure of geminiviruses provided useful insights into the mode of nucleic acid binding and the role of genome during capsid assembly. The online version contains supplementary material available at 10.1007/s13205-022-03204-4.
- |||||||||| entecavir / Generic mfg.
Review, Journal: How to achieve functional cure of HBV: Stopping NUCs, adding interferon or new drug development? (Pubmed Central) - May 27, 2022 The development of curative HBV therapies should be coupled with the development of standardised and validated virologic and immunologic assays to confirm target engagement and to assess response. In addition to efficacy, curative therapies must be safe and affordable to meet the goal of global elimination of hepatitis B.
- |||||||||| Journal: Transient RNA Interactions Leave a Covalent Imprint on a Viral Capsid Protein. (Pubmed Central) - May 20, 2022
In particular, it enables the redox-dependent regulation of the exposure of the C-terminal extension on the capsid surface, which is required for nuclear uptake of the capsid. Phylogenetic analysis of capsid proteins from hepadnaviruses points toward a function of this switch in the persistence of HBV infections.
- |||||||||| Preclinical, Journal: Dysregulation of Hepatitis B Virus Nucleocapsid Assembly in vitro by RNA-binding Small Ligands. (Pubmed Central) - May 12, 2022
This also allows for computational exploration of potential synergic effects between anti-viral ligands directed at distinct molecular targets in vivo. HBV PS-regulated assembly can be dysregulated by novel small molecule RNA-binding ligands opening a novel target for developing directly-acting anti-virals against this major pathogen.
- |||||||||| The discovery of AMS-I-1274, a high potent and orally active capsid-assembly modulator against hepatitis B virus (Poster Area) - May 12, 2022 - Abstract #EASLILC2022EASL_ILC_2303;
HBV DNA was suppressed and maintained 2 log10- copies/ml below baseline after the cessation of RO7049389, which may suggest a certain level of suppression in cccDNA level/ transcriptional activity in treatment naïve patients. Taken together, these data support that AMS-I-1274 is a novel class II capsid inhibitor with high anti-HBV potency and a favorable preclinical profile for clinical advancement.
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