- |||||||||| bepirovirsen (GSK3228836) / GSK, canocapavir (ZM-H1505R) / Zhimeng Biopharma
Review, Journal: Emerging Trends and Future Directions in the Development of Anti-hepatitis B Therapies: A Horizon Scanning Review. (Pubmed Central) - Sep 17, 2025
The robust and diverse pipeline of novel anti-hepatitis B virus treatments offers promise for improving functional cure rates, but definitive conclusions await longer off-treatment follow-up and durability data. Continued research, rational combination strategies, and global collaboration are crucial to overcome challenges and ensure equitable access to these transformative therapies worldwide.
- |||||||||| Journal: Capsid redirection mechanism of the Staphylococcus aureus pathogenicity island SaPIpT1028. (Pubmed Central) - Sep 4, 2025
This work highlights SaPI adaptation, exemplified by Rcm's ability to exploit phages resistant to other remodellers, while inhibiting their reproduction. These findings underscore the dynamic co-evolution of phages and SaPIs, with Rcm playing a pivotal role in capsid size regulation and phage interference.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
- |||||||||| Journal: Exploring the Structural Divergence of HIV and SRLV Lentiviral Capsids. (Pubmed Central) - Aug 29, 2025
Furthermore, key regions of host factor interaction, such as the CypA binding motifs, have diverged in the SRLV CA assemblies. Our results contribute to understanding the SRLV lentiviral capsids which may facilitate structure-based inhibitor design strategies.
- |||||||||| entecavir / Generic mfg., neracorvir (GST-HG141) / Fujian Cosunter
Clinical, P2 data, Journal: Safety and efficacy of GST-HG141, a novel HBV capsid assembly modulator, for the treatment of chronic hepatitis B patients with low-level viremia: a randomized, double-blind, placebo-controlled, multicenter phase II study. (Pubmed Central) - Aug 14, 2025
P2
These results support the further development of GST-HG141 as a novel therapeutic option for CHB patients inadequately responding to conventional NUC treatment. This work was supported by the Fujian Akeylink Biotechnology Co., Ltd.
- |||||||||| Journal: Measuring the selective packaging of RNA molecules by viral coat proteins in cells. (Pubmed Central) - Aug 11, 2025
Our results rule out a longstanding model in which selective packaging requires the well-known translational repressor (TR) stem-loop, and instead support more recent models in which selectivity emerges from the collective interactions of multiple coat proteins and multiple stem-loops distributed across the RNA molecule. These findings establish a framework for studying and understanding selective packaging in a range of natural viruses and virus-like particles, and lay the groundwork for engineering synthetic systems that package specific RNA cargoes.
- |||||||||| Journal: Computer Simulations Show That Liquid-Liquid Phase Separation Enhances Self-Assembly. (Pubmed Central) - Aug 10, 2025
Moreover, long-lived aberrant off-pathway assembly intermediates can suppress yields within condensates. In addition to elucidating condensate-mediated assembly of viruses and other biological structures, these results may guide the use of condensates as a generic route to enhance and control self-assembly in human-engineered systems.
- |||||||||| Review, Journal: Baculovirus dual-phase infection strategy and biotechnological applications: A structural and regulatory review. (Pubmed Central) - Aug 7, 2025
This review synthesizes current knowledge on AcMNPV's lifecycle, structural components, and gene functions, while exploring engineered strategies to enhance its efficacy as a biopesticide and biomedical tool. This effort seeks to connect fundamental virology with translational discoveries by integrating mechanistic insights and developing applications, tackling issues of specificity, efficiency, and safety for sustainable solutions in agriculture and medicine.
- |||||||||| bepirovirsen (GSK3228836) / GSK
Review, Journal: Advancing HIV cure: insights from developing chronic hepatitis b therapies for functional cure. (Pubmed Central) - Aug 7, 2025
This effort seeks to connect fundamental virology with translational discoveries by integrating mechanistic insights and developing applications, tackling issues of specificity, efficiency, and safety for sustainable solutions in agriculture and medicine. Given the persistence of cccDNA and integrated DNA, together with HBsAg-induced immune dysfunction, successful treatment for CHB to induce FC is likely to require a combination of agents that inhibit viral replication, reduce HBsAg levels, and boost the antiviral immune response.
- |||||||||| Journal: Improving HEK293-based AAV-production using GSMMs, and a multi-omics approach. (Pubmed Central) - Jul 16, 2025
This trade-off is significant because it highlights a key challenge in AAV production: achieving a balance between capsid assembly and genome packaging to optimize the yield of functional viral vectors. Overall this suggests that while HIF1alpha inhibition enhances capsid assembly, it simultaneously hampers nucleotide synthesis via the pentose phosphate pathway (PPP), necessary for nucleotide synthesis, and therefore for AAV genome replication.
- |||||||||| Journal: Structural insights into scaffold-guided assembly of the Pseudomonas phage D3 capsid. (Pubmed Central) - Jul 15, 2025
Following scaffold digestion, the MCP capsid domains form strong interactions that maintain capsid structure throughout maturation. The scaffold constraints appear critical for capsid size determination and provide important understanding of the factors governing capsid assembly in general and expands our understanding of these ecologically and biomedically important viruses.
- |||||||||| Review, Journal: New therapeutic strategies against B and D hepatitis (Pubmed Central) - Jul 7, 2025
In addition to the strategies used for HBV, molecules targeting HDV entry or HDAg prenylation are currently being evaluated. We review the main characteristics of HBV and HDV viral replication and highlight the results obtained in clinical trials using the most advanced molecules developed to overcome these infections.
- |||||||||| morphothiadine mesilate (GLS4) / HEC Pharm
Journal: Discovery and mechanism verification of first-in-class hydrophobic tagging-based degraders of HBV core protein. (Pubmed Central) - Jun 9, 2025
Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.
- |||||||||| Journal: The central pore of HIV-1 capsomers promotes sustained stability of the viral capsid. (Pubmed Central) - Jun 6, 2025
Comparative analysis of several central pore mutants lacking the R18 ring revealed that particle infectivity was not correlated with IP6 binding or capsid assembly, but rather with capsid stability and key post-entry events including reverse transcription and nuclear entry. Our results indicate that the central pore plays critical roles in both the assembly of capsids and their sustained stability post-entry.
- |||||||||| 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) - May 29, 2025
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. Finally, we demonstrate analytically and numerically that the relative change of HBV RNA more accurately reflects the antiviral effectiveness of a CAM than the relative change in HBV DNA.
- |||||||||| Review, Journal: How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid. (Pubmed Central) - May 28, 2025
Indeed, such is the dependence of HIV-1 on IP6 that the virus actively packages it into virions during production. These discoveries have stimulated work from multiple labs into the role and importance of IP6 in HIV-1 replication, and is the subject of this review.
- |||||||||| Journal: Unraveling the Role of Mutations Outside the Basal Promoter and Precore Regions in the HBeAg-Negative Stage of Chronic Hepatitis B. (Pubmed Central) - May 22, 2025
Infectious clones generated from these genomes, each carrying between 21 and 66 amino acid substitutions, were characterized, showing that mutations in this stage differentially affected viral fitness in vitro by up- or downregulating HBV-DNA levels (ranging from 0.2 to 5 times those of the wild-type isolate), modulating capsid assembly, and altering the expression, secretion, and subcellular localization of viral proteins. In conclusion, while mutations in the BCP and precore regions are the primary drivers of HBeAg seroconversion, mutations outside these regions significantly influence HBV biology and potentially contribute to viral pathogenicity, underscoring the complex interplay between host and virus during the HBeAg-negative stage of chronic infection.
- |||||||||| Review, Journal: Mysteries of adenovirus packaging. (Pubmed Central) - May 20, 2025
We anticipate that lessons learned from adenovirus packaging will be highly valuable for the advancement of viral vectors and gene-delivery technologies. In reviewing this topic, we hope to stimulate discussion and facilitate future investigation that will ultimately resolve gaps in knowledge and expand our understanding of DNA virus genome packaging.
- |||||||||| Review, Journal: Hepatitis B Virus Nucleocapsid Assembly. (Pubmed Central) - May 3, 2025
It also highlights the contribution of cellular and cell-free systems to these discoveries and underscores the need for new approaches that reconstitute the complete HBV nucleocapsid assembly process. With the growing interest in developing nucleocapsid assembly inhibitors, some of which are currently in clinical trials, targeting Pol-pgRNA interactions and nucleocapsid assembly represents a promising therapeutic strategy for curing chronic hepatitis B.
- |||||||||| Review, Journal: Dynamic Allostery: Evolution's Double-Edged Sword in Protein Function and Disease. (Pubmed Central) - Apr 27, 2025
We demonstrate applications of these principles in understanding viral evolution, drug resistance, and capsid assembly dynamics. Understanding dynamic allostery provides critical insights into protein evolution and offers new avenues for therapeutic interventions targeting allosteric regulation.
- |||||||||| Review, Journal: Structural studies of Parvoviridae capsid assembly and evolution: implications for novel AAV vector design. (Pubmed Central) - Apr 17, 2025
Along with the structure and evolution of the Parvoviridae capsids, computational methods have provided significant insights into the design of novel AAV vector techniques, which include (a) Structure-guided design of AAV capsids with improved properties, (b) Directed Evolution of AAV capsids for specific applications, and (c) Computational prediction of AAV capsid-receptor interactions. Further discussion addressed the ongoing challenges in the AAV vector design and proposed future directions for exploring enhanced computational tools, such as artificial intelligence/machine learning and deep learning.
- |||||||||| Journal: Research Status and Applications of Adeno-Associated Virus. (Pubmed Central) - Apr 16, 2025
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.
- |||||||||| Addressing the Manufacturing Bottleneck in Gene Therapies Through AAV Production in Whole Nicotiana benthamiana Plants (Exhibit Theater) - Apr 10, 2025 - Abstract #ASGCT2025ASGCT_1704;
This method preserves the natural stoichiometry of AAV vectors, prevents toxicity from overexpression, and reduces recombination issues, resulting in more consistent vector production. Moreover, the split-Cap system potentially allows for the creation of hybrid AAV vectors by mixing and matching VP1, VP2, and VP3 proteins from various serotypes, which could improve tropism and immune evasion in future applications.
- |||||||||| Evolving Synthetic Membrane Associated Accessory Proteins (synMAAPs) for Enhanced AAV Vector Egress (New Orleans Theater A) - Apr 10, 2025 - Abstract #ASGCT2025ASGCT_1051;
In addition to dissecting the biology of AAV egress, we integrate these findings into engineered AAV vector production workflows, demonstrating the potential for improved secretion and streamlined manufacturing eliminating the need for cell lysis, reducing host cell contaminants and potentially enabling continuous perfusion systems. Disease Focus of Abstract:None
- |||||||||| Journal: Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly. (Pubmed Central) - Apr 1, 2025
Here we employ the Weighted Ensemble methodology to characterize the free-energy landscape of our earlier determined functionally relevant progress coordinates. It is shown that this approach provides conformations outside those sampled by standard MD, as well as an increased number of structures with correspondingly enlarged binding pockets conducive to ligand binding, illustrating the utility of Weighted Ensemble for computational drug development.
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