-
Bioorganic & Medicinal Chemistry Letters Nov 2021The HBV core protein serves multiple essential functions in the viral life cycle that enable chronic HBV infection to persist, and as such, represents a promising drug...
The HBV core protein serves multiple essential functions in the viral life cycle that enable chronic HBV infection to persist, and as such, represents a promising drug target. Modulation of the HBV capsid assembly has shown efficacy in early clinical trials through use of small molecule capsid assembly modulators (CAMs). Herein is described the evolution and SAR of a novel pyrazolo piperidine lead series into advanced oxadiazepinone HBV CAMs.
Topics: Antiviral Agents; Azepines; Capsid Proteins; Dose-Response Relationship, Drug; Hepatitis B virus; Humans; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship
PubMed: 34492302
DOI: 10.1016/j.bmcl.2021.128353 -
Viruses Nov 2022Endoplasmic reticulum (ER) stress, a type of cellular stress, always occurs when unfolded or misfolded proteins accumulating in the ER exceed the protein folding... (Review)
Review
Endoplasmic reticulum (ER) stress, a type of cellular stress, always occurs when unfolded or misfolded proteins accumulating in the ER exceed the protein folding capacity. Because of the demand for rapid viral protein synthesis after viral infection, viral infections become a risk factor for ER stress. The hepatocyte is a cell with large and well-developed ER, and hepatitis virus infection is widespread in the population, indicating the interaction between hepatitis viruses and ER stress may have significance for managing liver diseases. In this paper, we review the process that is initiated by the hepatocyte through ER stress against HBV and HCV infection and explain how this information can be helpful in the treatment of HBV/HCV-related diseases.
Topics: Humans; Hepatitis B virus; Hepacivirus; Unfolded Protein Response; Endoplasmic Reticulum Stress; Hepatitis C
PubMed: 36560634
DOI: 10.3390/v14122630 -
Zhonghua Gan Zang Bing Za Zhi =... May 2022Most patients with early stage chronic hepatitis B virus infection are in the immune-tolerant phase. Therefore, previously been generally believed that there is no... (Review)
Review
Most patients with early stage chronic hepatitis B virus infection are in the immune-tolerant phase. Therefore, previously been generally believed that there is no disease progression or liver injury-related events, and poor antiviral efficacy in patients with immune-tolerant phase. With that in mind, antiviral therapy is generally not recommended in current domestic and foreign guidelines. However, more and more studies have shown that patients in the immune-tolerant phase may develop liver cirrhosis and hepatocellular carcinoma without treatment, so clinical treatment is urgently needed. Currently, drugs based on nucleocapsid inhibitor, immune modulation, and other novel mechanisms for viral replication are being developed to reduce hepatitis B surface antigen, which offers the possibility to achieve viral suppression or even functional cure in these patients. This paper mainly reviews and discusses the latest research progress, population characteristics, treatment needs, and design strategies of clinical trials of new drug for immune-tolerant phase population.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Neoplasms
PubMed: 35764552
DOI: 10.3760/cma.j.cn501113-20211220-00606 -
Frontiers in Immunology 2023
Topics: Antiviral Agents; Hepatitis B virus; Interferon-alpha; Hepatocytes
PubMed: 36817476
DOI: 10.3389/fimmu.2023.1135649 -
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 -
Psychology, Health & Medicine Sep 2022Stigma related to hepatitis B virus (HBV) has a detrimental impact on health outcomes of people living with HBV. A scoping review of published peer-reviewed articles... (Review)
Review
Stigma related to hepatitis B virus (HBV) has a detrimental impact on health outcomes of people living with HBV. A scoping review of published peer-reviewed articles focused on the Chinese population in mainland China published between 2010 and 2019 was undertaken. This review consists of five stages: identifying the research question, identifying relevant literature, study selection, charting the data, and collating, summarizing and reporting the results. Articles in Chinese were identified from the collection of Core Journals in the database of CNKI (China Academic Journals Full-text Database). Publications in English were identified in Global Health, Scopus, PsycINFO, Proquest and Web of Science. Forty-five peer-reviewed articles were selected for inclusion. Most studies under review focused on negative individual attitude and discrimination against people living with HBV (PLHBV) in employment, education, community and healthcare settings. There is limited information on lived experiences of those living with HBV and how they manage this stigma. The reviewed studies provide evidence for the existence of different forms of HBV-related stigma in a variety of settings. Knowledge about HBV and the level of education of research participants were the most frequently identified factors related to this stigma. These findings are useful to support HBV responses in China and countries with migration from China.
Topics: Asian People; Bibliometrics; China; Hepatitis B virus; Humans; Social Stigma
PubMed: 34190017
DOI: 10.1080/13548506.2021.1944651 -
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 -
Journal of Virology Oct 2023Chronic hepatitis B is the most important cause of liver cancer worldwide and affects more than 290 million people. Current treatments are mostly suppressive and rarely...
Chronic hepatitis B is the most important cause of liver cancer worldwide and affects more than 290 million people. Current treatments are mostly suppressive and rarely lead to a cure. Therefore, there is a need for novel and curative drugs that target the host or the causative agent, hepatitis B virus itself. Capsid assembly modulators are an interesting class of antiviral molecules that may one day become part of curative treatment regimens for chronic hepatitis B. Here we explore the characteristics of a particularly interesting subclass of capsid assembly modulators. These so-called non-HAP CAM-As have intriguing properties in cell culture but also clear virus-infected cells from the mouse liver in a gradual and sustained way. We believe they represent a considerable improvement over previously reported molecules and may one day be part of curative treatment combinations for chronic hepatitis B.
Topics: Animals; Humans; Mice; Antiviral Agents; Capsid; Capsid Proteins; Cells, Cultured; Hepatitis B virus; Hepatitis B, Chronic; In Vitro Techniques; Virus Assembly; Disease Models, Animal
PubMed: 37754761
DOI: 10.1128/jvi.00722-23 -
JAMA Network Open Jul 2023
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Hepatitis B virus; Embryo Transfer; Pregnancy Rate; Hepatitis B
PubMed: 37450305
DOI: 10.1001/jamanetworkopen.2023.23495