Ligand-based pharmacophore modeling, virtual screening, and 2D quantitative structure-activity relationship performance on anti-Hepatitis B virus flavonols DOI Open Access
Alireza Mohebbi, Fatemeh Sana Askari,

Parnia Askari

et al.

Published: March 28, 2024

Background: Targeting Hepatitis B virus (HBV) infection in human is crucial due to its adverse. Herbal medicine has long been significant this regard, with flavonoids demonstrating promising results. Hence, establishing a way of identifying anti-HBV activities the aim present study. Methods: Flavonoid structures 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. Applicability domain (AD) defined Euclidean distance calculations for validation. Results: The best model, consisting 57 features generated. HTS resulted 509 unique hits. model's sensitivity specificity 71% 100%, respectively. two predictors, x4a qed, exhibited strong predictive performance an adjusted-R² value 0.85 0.90 Q2. Conclusion: separate chemical sets, guaranteeing reproducibility usefulness other flavonols by utilizing characteristics X4A qed. These results provide new possibilities discovering future drugs integrating modeling experimental research.

Language: Английский

Pharmacophore modeling and QSAR analysis of anti-HBV flavonols DOI Creative Commons

Basireh Baei,

Parnia Askari,

Fatemeh Sana Askari

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0316765 - e0316765

Published: Jan. 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.

Language: Английский

Citations

3
Mechanism of interferon alpha therapy for chronic hepatitis B and potential approaches to improve its therapeutic efficacy DOI
Qiong Zhao, Hui Liu,

Liudi Tang

et al.

Antiviral Research, Journal Year: 2023, Volume and Issue: 221, P. 105782 - 105782

Published: Dec. 17, 2023

Language: Английский

Citations

28
Integrated HBV DNA and cccDNA maintain transcriptional activity in intrahepatic HBsAg‐positive patients with functional cure following PEG‐IFN‐based therapy DOI
Na Gao, Guiwen Guan,

Ganlin Xu

et al.

Alimentary Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 58(10), P. 1086 - 1098

Published: Aug. 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

Language: Английский

Citations

18
Review of Related Factors for Persistent Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma DOI Open Access
Nevin Varghese,

Amry Majeed,

Suraj Nyalakonda

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 777 - 777

Published: Feb. 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.

Language: Английский

Citations

8
Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies DOI Creative Commons
Hui Ma,

Qing-Zhu Yan,

Jingru Ma

et al.

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(10), P. 1295 - 1312

Published: March 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

Language: Английский

Citations

8
Current and emerging strategies for the prevention of hepatocellular carcinoma DOI
Yee Hui Yeo, Manal F. Abdelmalek, Seema A. Khan

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 22(3), P. 173 - 190

Published: Dec. 9, 2024

Language: Английский

Citations

7
Prospects for Controlling Hepatitis B Globally DOI Creative Commons
Vincent Soriano, Víctor Moreno‐Torres, Ana Treviño

et al.

Pathogens, Journal Year: 2024, Volume and Issue: 13(4), P. 291 - 291

Published: March 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.

Language: Английский

Citations

5
The Discovery and Preclinical Profile of ALG-000184, a Prodrug of the Potent Hepatitis B Virus Capsid Assembly Modulator ALG-001075 DOI

Sandrine Vendeville,

Franck Amblard,

Leda Bassit

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

Citations

5
Management of Hepatitis B Virus and Hepatitis C Virus Infections in Patients with Cancer Receiving Immune Checkpoint Inhibitors DOI Creative Commons
Khalis Mustafayev, Vincent Mallet, Harrys A. Torres

et al.

Journal of Immunotherapy and Precision Oncology, Journal Year: 2024, Volume and Issue: 7(2), P. 111 - 121

Published: Jan. 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.

Language: Английский

Citations

4
mRNA Therapeutic Vaccine for Hepatitis B Demonstrates Immunogenicity and Efficacy in the AAV-HBV Mouse Model DOI Creative Commons
Dorien De Pooter, Wim Pierson, Soheil Pourshahian

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(3), P. 237 - 237

Published: Feb. 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

Language: Английский

Citations

4