Pharmacophore modeling and QSAR analysis of anti-HBV flavonols

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0316765 - e0316765

Опубликована: Янв. 13, 2025

Due to its global burden, Targeting Hepatitis B virus (HBV) infection in humans is crucial. Herbal medicine has long been significant, with flavonoids demonstrating promising results. Hence, the present study aimed establish a way of identifying anti-HBV activities. Flavonoid structures activities were retrieved. A flavonol-based pharmacophore model was established using LigandScout v4.4. Screening performed PharmIt server. QSAR equation developed and validated independent sets compounds. The applicability domain (AD) defined Euclidean distance calculations for validation. best model, consisting 57 features, generated. High-throughput screening (HTS) resulted 509 unique hits. model's accuracy further set FDA-approved chemicals, sensitivity 71% specificity 100%. Additionally, two predictors, x4a qed, exhibited predictive solid performance an adjusted-R2 value 0.85 0.90 Q2. PCA showed essential patterns relationships within dataset, first components explaining nearly 98% total variance. Current HBV therapies tend fail provide complete cure, emphasizing need new therapies. This study's importance highlight flavonols as potential medicines, presenting supplementary option existing therapy. separate chemical sets, guaranteeing reproducibility usefulness other by utilizing characteristics X4A qed. These results possibilities discovering future drugs integrating modeling experimental research.

Язык: Английский

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Mechanism of interferon alpha therapy for chronic hepatitis B and potential approaches to improve its therapeutic efficacy

Antiviral Research, Год журнала: 2023, Номер 221, С. 105782 - 105782

Опубликована: Дек. 17, 2023

Язык: Английский

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Integrated HBV DNA and cccDNA maintain transcriptional activity in intrahepatic HBsAg‐positive patients with functional cure following PEG‐IFN‐based therapy

Alimentary Pharmacology & Therapeutics, Год журнала: 2023, Номер 58(10), С. 1086 - 1098

Опубликована: Авг. 29, 2023

Summary Background Hepatitis B surface antigen (HBsAg) seroclearance marks regression of hepatitis virus (HBV) infection. However, more than one‐fifth patients with functional cure following pegylated interferon‐based therapy may experience HBsAg seroreversion. The mechanisms causing the HBV relapse remain unclear. Aim To investigate level and origin transcripts in their role predicting relapse. Methods Liver tissue obtained from cure, as well uncured treatment‐naïve HBeAg‐negative chronic (CHB) were analysed for intrahepatic markers. capture RNA sequencing used to detect integration chimeric transcripts. Results Covalently closed circular DNA (cccDNA) levels proportion HBsAg‐positive hepatocytes functionally cured significantly lower those patients. Integrated declined compared present 25.5% patients, while remained 72.2%. RNA, integrated DNA, higher without. residual was mainly derived transcriptionally active DNA; meanwhile, trace transcriptional activity cccDNA could also remain. Two out four experienced Conclusion maintain maybe involved seroreversion linked virological

Язык: Английский

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Review of Related Factors for Persistent Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma

Cancers, Год журнала: 2024, Номер 16(4), С. 777 - 777

Опубликована: Фев. 14, 2024

Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing DNA levels become undetectable. However, literature has that some patients persistent risk developing HCC. The mechanism this occurs not fully elucidated. it discovered HBV’s covalently closed circular (cccDNA) integrates into critical HCC driver genes hepatocytes upon initial infection; additionally, these are targets current NA therapies. Some studies suggest undergoes compartmentalization peripheral blood mononuclear cells serve as a sanctuary for replication during antiviral therapy. aim review expand on how with may develop despite years viral suppression carry worse prognosis than treatment-naive who Furthermore, recurrence after surgical or locoregional setting carcinogenic behave more aggressively treatment. Curative novel therapies target life cycle HBV, modulate host immune response, inhibit RNA translation being investigated.

Язык: Английский

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Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

World Journal of Gastroenterology, Год журнала: 2024, Номер 30(10), С. 1295 - 1312

Опубликована: Март 14, 2024

Hepatitis B virus (HBV) reactivation is a clinically significant challenge in disease management. This review explores the immunological mechanisms underlying HBV reactivation, emphasizing progression and It delves into host immune responses reactivation’s delicate balance, spanning innate adaptive immunity. Viral factors’ disruption of this as are interactions between viral antigens, cells, cytokine networks, checkpoint pathways, examined. Notably, roles T natural killer antigen-presenting cells discussed, highlighting their influence on progression. impact severity, hepatic flares, liver fibrosis progression, hepatocellular carcinoma detailed. Management strategies, including anti-viral immunomodulatory approaches, critically analyzed. The role prophylactic therapy during immunosuppressive treatments explored alongside novel immunotherapeutic interventions to restore control prevent reactivation. In conclusion, comprehensive furnishes holistic view that propel With dedicated focus understanding its implications for prospects efficient management article contributes significantly knowledge base. more profound insights intricate elements system will inform evidence-based ultimately enhancing elevating patient outcomes. dynamic landscape strategies scrutinized, approaches. preventing potential innovative proactively deter

Язык: Английский

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Current and emerging strategies for the prevention of hepatocellular carcinoma

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2024, Номер 22(3), С. 173 - 190

Опубликована: Дек. 9, 2024

Язык: Английский

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The Discovery and Preclinical Profile of ALG-000184, a Prodrug of the Potent Hepatitis B Virus Capsid Assembly Modulator ALG-001075

Journal of Medicinal Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 22, 2024

Chronic hepatitis B (CHB) represents a significant unmet medical need with few options beyond lifelong treatment nucleoside analogues, which rarely leads to functional cure. Novel agents that reduce levels of HBV DNA, RNA and other viral antigens could lead better outcomes. The capsid assembly modulator (CAM) class compounds an important modality for chronic suppression improve cure rates, either alone or in combination.

Язык: Английский

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Prospects for Controlling Hepatitis B Globally

Pathogens, Год журнала: 2024, Номер 13(4), С. 291 - 291

Опубликована: Март 29, 2024

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic B, and more than 800,000 patients die each year due to complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage suboptimal. In adults, sexual transmission by far most frequent route of contagion. The WHO estimates that 1.5 new infections occur annually. Oral nucleos(t)ide analogues entecavir tenofovir antivirals prescribed as therapy. Almost adherent medication achieve undetectable plasma viremia beyond 6 months monotherapy. However, less 5% anti-HBs seroconversion, viral rebound occurs following drug discontinuation. Therefore, need be lifelong. New long-acting formulations being developed will maximize treatment benefit overcome adherence barriers. Furthermore, antiviral agents in development, entry inhibitors, capside assembly modulators, RNA interference molecules. use combination therapy pursues a functional cure, meaning it negative both circulating HBV-DNA HBsAg. Even when this goal achieved, cccDNA reservoir within infected hepatocytes remains signal past infection, can reactivate under immune suppression. gene therapies, editing, eagerly pursued silence or definitively disrupt genomes and, way, ultimately cure B. At time, three actions taken push eradication globally: (1) expand universal newborn vaccination; (2) perform once-in-life testing adults identify susceptible persons could vaccinated (or re-vaccinated) unveil asymptomatic carriers treatment; (3) provide earlier carriers, aviremic reduces risk clinical progression transmission.

Язык: Английский

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Management of Hepatitis B Virus and Hepatitis C Virus Infections in Patients with Cancer Receiving Immune Checkpoint Inhibitors

Journal of Immunotherapy and Precision Oncology, Год журнала: 2024, Номер 7(2), С. 111 - 121

Опубликована: Янв. 12, 2024

ABSTRACT Background Patients with cancer hepatitis B virus (HBV) or C (HCV) infection are excluded from many clinical trials of immune checkpoint inhibitors (ICIs). Therefore, data limited regarding the management HBV and HCV infections in patients treated ICIs. To address this gap, we reviewed literature on receiving Methods We searched MEDLINE PubMed for all original research articles, case reports, systematic reviews published English between Jul 2013 2023 Results found 28 studies (three prospective trials, seven retrospective cohort studies, nine series, reports) that evaluated safety ICI therapy cancer. The overall rate reactivation was 1.4% (38/2799), no HBV-related deaths were reported. frequency chronic past 2% (35/1667) 0.3% (3/1132), respectively. risk significantly higher among not antiviral prophylaxis than those antivirals (17% vs 1%, p < 0.05). Based high-quality evidence, infection, is recommended before initiation. For monitoring on-demand treatment sufficient. 11 (five five one observational study) 0.5% (2/387), HCV-related occurs primarily immunosuppressants ICI-related toxic effects. ICIs safe HCV-infected solid tumors. Conclusions Chronic should be considered a contraindication therapy. Specific assessment, monitoring, strategies necessary to reduce liver injury infection.

Язык: Английский

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mRNA Therapeutic Vaccine for Hepatitis B Demonstrates Immunogenicity and Efficacy in the AAV-HBV Mouse Model

Vaccines, Год журнала: 2024, Номер 12(3), С. 237 - 237

Опубликована: Фев. 25, 2024

Chronic infection with hepatitis B virus (HBV) develops in millions of patients per year, despite the availability effective prophylactic vaccines. Patients who resolve acute HBV develop HBV-specific polyfunctional T cells accompanied by neutralizing antibodies, while chronic (CHB), immune are dysfunctional and impaired. We describe a lipid nanoparticle (LNP)-formulated mRNA vaccine, optimized for expression core, polymerase, surface (preS2-S) antigens aim inducing an response CHB. Prime prime/boost vaccination LNP-formulated encoding pol, and/or preS2-S dosing strategies were compared naive C57BL/6 BALB/c mice. Immune responses assessed IFN-γ ELISpot, intracellular cytokine staining (ICS), ELISA antibody production, whereas anti-viral efficacy was evaluated AAV-HBV mouse model. The vaccine induced strong antigen-specific cell these models, emergence anti-HBs anti-HBe antibodies. After three immunizations, stimulation resulted up to 1.7 log

Язык: Английский

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