- |||||||||| Review, Journal: Small Molecule HBV RNA Destabilizing Drugs: Drugs of the Future or Compounds from the Past? (Pubmed Central) - Nov 30, 2025
Yet, with the apparent success of other investigational antivirals in reducing HBsAg levels, such as siRNAs, antisense oligonucleotides, and in at least one example, capsid assembly modulators (CAMs), questions remain as to whether RNA destabilizers still have a role in managing chronic hepatitis B (CHB). This review describes the current status of PAPD5/7 inhibitor development, evaluates the advantages and limitations of the approach, and considers potential strategies for integrating this class of molecules with other HBV therapies.
- |||||||||| Journal: UBE2O, a host ubiquitin-conjugating enzyme, is a key regulator of Hepatitis B virus maturation and egress. (Pubmed Central) - Nov 28, 2025
Subcellular localization experiments using confocal microscopy and proximity ligation assays (PLA) demonstrated that UBE2O colocalizes with capsids and ubiquitinated cargo in CD63-positive MVB compartments, indicating its involvement in the endosomal secretory pathway. Collectively, this study identifies UBE2O and its catalytic activity as key regulators of the HBV virion secretion pathway, highlighting its potential as a therapeutic target for HBV treatment.
- |||||||||| ALG-000184 / Aligos Therap
Capsid Assembly Modulator ALG-001075 Binds and Directly Targets HBeAg (Convention Center: Hall DE 1118-1367 Posters) - Oct 7, 2025 - Abstract #AASLD2025AASLD_1394;
ALG-001075 demonstrated direct binding to HBeAg and pronounced in vitro reductions in secreted HBeAg levels, in line with clinical observations for its prodrug ALG-000184, suggesting direct inhibition of HBeAg as a third mechanism of action for ALG-001075. Although the direct HBeAg effect requires higher compound concentrations than the primary and secondary effects of CAMs, the high pharmacokinetic exposure achieved with prodrug ALG-000184 and relative HBeAg-targeting potency of parent ALG-001075 likely enable the clinical observation of this effect.
- |||||||||| CAM-E and CAM-A Compounds Differentially Affect Phosphorylated and Non-Phosphorylated Hepatitis B Core Protein In Vitro (Convention Center: Hall DE 1118-1367 Posters) - Oct 7, 2025 - Abstract #AASLD2025AASLD_1386;
The observed concentration-dependent effects of CAM-A compounds on P-HBcAg levels suggest a nuanced interaction that may involve capturing P-HBcAg in intracellular aggregates at higher concentrations. The lack of direct impact by nucleos(t)ide analogs on HBcAg and P-HBcAg levels is in line with their known mechanism of action and underscores the specificity of CAMs in targeting HBc.
- |||||||||| ALG-000184 / Aligos Therap
Capsid Assembly Modulator ALG-001075 Prevents cccDNA Formation and HBV DNA Integration In Vitro (Convention Center: Hall DE 1118-1367 Posters) - Oct 7, 2025 - Abstract #AASLD2025AASLD_1307;
ALG-000184 is a prodrug of ALG-001075, a novel capsid assembly modulator leading to the formation of empty capsids (CAM-E)...This was not the case for nucleos(t)ide analogs entecavir and tenofovir... ALG-001075 demonstrated potent prevention of HBV cccDNA formation and HBV DNA integration, further confirming its best-in-class properties and superiority over commonly used nucleos(t)ide analogs.
- |||||||||| CORE PROTEIN MUTATIONS IN HBSAG/HBV DNA DOUBLE-NEGATIVE OCCULT HEPATITIS B INFECTION AND THEIR BIDIRECTIONAL REGULATION ON VIRAL REPLICATION (Convention Center: Hall DE 1118-1367 Posters) - Oct 7, 2025 - Abstract #AASLD2025AASLD_1223;
These findings suggest that dual oral therapy with SAG-524 and CBT-209 holds promise as a strategy to achieve a functional cure for chronic hepatitis B. A58V+S74N mutation can promote virus transcription and protein expression, while other mutations suppress virus replication to varying degrees.Among them, A11V+L119P and V13M mutations may destroy the capsid assembly interaction between HBsAg and HBcAg, and E64G mutation may be related to X gene regulation.
- |||||||||| Review, Journal: 25 years of Ebola Virus VP35 Research. (Pubmed Central) - Oct 1, 2025
Here, we will provide a comprehensive review of the VP35 structure and known insights into function. Given its significant role, VP35 has also emerged as a therapeutic target for the development of countermeasures.
- |||||||||| 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 27, 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.
- |||||||||| Review, Journal: The Triplex-Centric Assembly and Maturation of the Herpesvirus Procapsid. (Pubmed Central) - Sep 27, 2025
Angularization of the capsid shifts the portal outward to a better contact with the capsid shell. Understanding these events in the herpesvirus life cycle to atomic detail could facilitate the development of drugs that uniquely target assembly and maturation.
- |||||||||| 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.
- |||||||||| Assessing the methylation state of recombinant AAV productions (Fibes 2) - Aug 21, 2025 - Abstract #ESGCT2025ESGCT_392;
Our results demonstrate the ability to detect and differentiate dam, dcm, and CpG methylation states within AAV encapsidated DNA using Nanopore sequencing. These findings provide new insights into the epigenetic composition of rAAV vector preparations and highlight the relevance of methylation status in influencing the immunogenic profile of gene therapy vectors.
- |||||||||| 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.
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