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International Journal of Infectious... Sep 2023
Topics: Humans; Hepatitis B virus; Mental Disorders
PubMed: 37507084
DOI: 10.1016/j.ijid.2023.07.028 -
ACS Infectious Diseases May 2019Hepatitis B virus (HBV) chronically infects >250 million people and kills nearly a million annually, and current antivirals cannot clear the infection or adequately... (Review)
Review
Hepatitis B virus (HBV) chronically infects >250 million people and kills nearly a million annually, and current antivirals cannot clear the infection or adequately suppress disease. The virus replicates by reverse transcription, and the dominant antiviral drugs are nucleos(t)ide analogs that target the viral reverse transcriptase. We are developing antivirals targeting the other essential viral enzymatic activity, the ribonuclease H (RNaseH). HBV RNaseH inhibitors with efficacies in the low micromolar to nanomolar range against viral replication in culture have been identified in the α-hydroxytropolone and hydroxyimide chemotypes. Here, we review the promise of RNaseH inhibitors, their current structure-activity relationships, and challenges to optimizing the inhibitors into leads for clinical assessment.
Topics: Antiviral Agents; Enzyme Inhibitors; Hepatitis B virus; Ribonuclease H; Structure-Activity Relationship; Virus Replication
PubMed: 29565562
DOI: 10.1021/acsinfecdis.8b00045 -
Frontiers in Cellular and Infection... 2022Numerous canonical cellular signaling pathways modulate hepatitis B virus (HBV) replication. HBV genome products are known to play a significant role in regulating these... (Review)
Review
Numerous canonical cellular signaling pathways modulate hepatitis B virus (HBV) replication. HBV genome products are known to play a significant role in regulating these cellular pathways for the liver's viral-related pathology and physiology and have been identified as the main factor in hepatocarcinogenesis. Signaling changes during viral replication ultimately affect cellular persistence, multiplication, migration, genome instability, and genome damage, leading to proliferation, evasion of apoptosis, block of differentiation, and immortality. Recent studies have documented that numerous signaling pathway agonists or inhibitors play an important role in reducing HBV replication and , and some have been used in phase I or phase II clinical trials. These optional agents as molecular therapeutics target cellular pathways that could limit the replication and transcription of HBV or inhibit the secretion of the small surface antigen of HBV in a signaling-independent manner. As principle-based available information, a combined strategy including antiviral therapy and immunomodulation will be needed to control HBV infection effectively. In this review, we summarize recent findings on interventions of molecular regulators in viral replication and the interactions of HBV proteins with the components of the various targeting cellular pathways, which may assist in designing novel agents to modulate signaling pathways to prevent HBV replication or carcinogenesis.
Topics: Hepatitis B; Hepatitis B virus; Humans; Signal Transduction; Virus Replication
PubMed: 35252042
DOI: 10.3389/fcimb.2022.847539 -
Infectious Disease Clinics of North... Jun 2020Hepatitis B virus (HBV) reactivation can be a serious complication for patients with chronic or resolved HBV infection when treated with biologics. For HBsAg-positive... (Review)
Review
Hepatitis B virus (HBV) reactivation can be a serious complication for patients with chronic or resolved HBV infection when treated with biologics. For HBsAg-positive patients receiving biologics, the risk of HBV reactivation is moderate to high. HBsAg-negative/anti-HBc positive patients are at lower risk of HBV reactivation than HBsAg-positive patients. However, patients taking anti-CD20 agents, such as rituximab, have high risk of HBV reactivation (>10%), so antiviral prophylactic therapies are required. This review provides the different classes of biologics associated with HBV reactivation, stratifies the various reactivation risk levels by HBV status and biologic agent, and discusses management strategies.
Topics: Antibiotic Prophylaxis; Biological Factors; Hepatitis B; Hepatitis B virus; Humans; Nucleosides; Precision Medicine; Virus Activation
PubMed: 32334985
DOI: 10.1016/j.idc.2020.02.009 -
Frontiers in Immunology 2023
Topics: Antiviral Agents; Hepatitis B virus; Interferon-alpha; Hepatocytes
PubMed: 36817476
DOI: 10.3389/fimmu.2023.1135649 -
Current Opinion in Virology Feb 2016The origin of primate HBV (family Hepadnaviridae) is unknown. Hepadnaviruses are ancient pathogens and may have been associated with old mammalian lineages like bats for... (Review)
Review
The origin of primate HBV (family Hepadnaviridae) is unknown. Hepadnaviruses are ancient pathogens and may have been associated with old mammalian lineages like bats for prolonged time. Indeed, the genetic diversity of bat hepadnaviruses exceeds that of extant hepadnaviruses in other host orders, suggesting a long evolution of hepadnaviruses in bats. Strikingly, a recently detected New World bat hepadnavirus is antigenically related to HBV and can infect human hepatocytes. Together with genetically diverse hepadnaviruses from New World rodents and a non-human primate, these viruses argue for a New World origin of ancestral orthohepadnaviruses. Multiple host switches of bat and primate viruses are evident and bats are likely sources of ancestral hepadnaviruses acquired by primates.
Topics: Animals; Chiroptera; Disease Reservoirs; Evolution, Molecular; Genetic Variation; Hepadnaviridae; Hepatitis B virus; Hepatitis, Viral, Animal; Host Specificity; Primates; Viral Tropism
PubMed: 26897577
DOI: 10.1016/j.coviro.2016.01.015 -
Hepatology (Baltimore, Md.) Apr 2023
Topics: Humans; Hepatitis B virus; Liver Cirrhosis
PubMed: 36626636
DOI: 10.1097/HEP.0000000000000031 -
Alimentary Pharmacology & Therapeutics Jan 2021
Topics: Antiviral Agents; Biomarkers; Hepatitis B Surface Antigens; Hepatitis B virus; Humans
PubMed: 33368512
DOI: 10.1111/apt.16171 -
Journal of Hepatology Oct 2022
Topics: CD8-Positive T-Lymphocytes; Hepatitis B virus; Hepatitis E; Hepatitis E virus; Humans
PubMed: 35977612
DOI: 10.1016/j.jhep.2022.08.002 -
Nature Reviews. Gastroenterology &... Sep 2022
Topics: Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans
PubMed: 35883011
DOI: 10.1038/s41575-022-00664-0