Article
Biochemistry & Molecular Biology
Gary Grosser, Simon Franz Mueller, Michael Kirstgen, Barbara Doering, Joachim Geyer
Summary: The study found that NTCP, ASBT, and SOAT share a common substrate, taurolithocholic acid, but have differences in substrate recognition and inhibitors. NTCP can be influenced by inhibitors such as the HBV/HDV-derived myr-preS1 peptide, with high affinity for taurocholic acid, dehydroepiandrosterone sulfate, and taurolithocholic acid.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Gastroenterology & Hepatology
David J. Matye, Huaiwen Wang, Wenyi Luo, Rachel R. Sharp, Cheng Chen, Lijie Gu, Kenneth L. Jones, Wen-Xing Ding, Jacob E. Friedman, Tiangang Li
Summary: Combining ASBT inhibitor and FGF15 signaling activation improves therapeutic efficacy against NASH by reducing bile acid burden in the liver and limiting intestinal lipid absorption. The synergistic actions of the two treatments produce weight loss, reduce adipose inflammation, and attenuate hepatocellular organelle stress. Further clinical studies are needed to explore the potential of this combined treatment in humans.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Virology
Dariusz Zakrzewicz, Regina Leidolf, Sebastian Kunz, Simon Franz Mueller, Anita Neubauer, Silke Leiting, Nora Goldmann, Felix Lehmann, Dieter Glebe, Joachim Geyer
Summary: Tyrosine 146 and to some extent tyrosine 141 of human NTCP play an essential role in the interaction of HBV with its receptor NTCP and the process of virus entry into hepatocytes.
Review
Microbiology
Hongbo Guo, Stephan Urban, Wenshi Wang
Summary: Chronic HBV and HDV infections pose a significant global health burden, and despite current treatments, complete viral eradication and cure is difficult due to the persistence of viral templates. Understanding the molecular biology of both viruses and their interaction with host cells is crucial for developing curative antiviral therapies. The discovery of the NTCP receptor has revolutionized HBV/HDV research, and recent advancements in cell culture models have provided new opportunities for studying these viruses. This review summarizes the available cell culture models, discusses their advantages and limitations, and highlights their potential for future HBV and HDV research.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Virology
Massimo Palatini, Simon Franz Mueller, Michael Kirstgen, Silke Leiting, Felix Lehmann, Lena Soppa, Nora Goldmann, Christin Mueller, Kira Alessandra Alicia Theresa Lowjaga, Jorg Alber, Giuliano Ciarimboli, John Ziebuhr, Dieter Glebe, Joachim Geyer
Summary: This study identified IFITM3 as a novel protein-protein interaction partner of NTCP, which significantly affects the infection of HBV and HDV in hepatoma cells and primary human hepatocytes expressing NTCP. However, the specific mechanism by which this interaction facilitates the infection process remains unknown.
Article
Gastroenterology & Hepatology
Roni F. Kunst, Dirk R. de Waart, Frank Wolters, Suzanne Duijst, Esther W. Vogels, Isabelle Bolt, Joanne Verheij, Ulrich Beuers, Ronald P. J. Oude Elferink, Stan F. J. van de Graaf
Summary: This study demonstrates that reducing the bile salt pool size effectively lowers cholestatic liver injury in mice. Systemic ASBT inhibition may be a valuable treatment for cholestatic liver disease by decreasing the pool size and increasing renal bile salt output, even under conditions of minimal fecal bile salt secretion.
Article
Virology
Michael Kirstgen, Kira Alessandra Alicia Theresa Lowjaga, Simon Franz Mueller, Nora Goldmann, Felix Lehmann, Dieter Glebe, Karl-Heinz Baringhaus, Joachim Geyer
Summary: This study identified virus-selective inhibitors of NTCP for HBV/HDV through screening different compounds, providing a novel approach for the development of cell-entry inhibitors.
Article
Pharmacology & Pharmacy
Maya Shofa, Akiho Ohkawa, Yasuyuki Kaneko, Akatsuki Saito
Summary: Domestic cat hepadnavirus (DCH), a novel hepadnavirus in cats, is genetically close to hepatitis B virus (HBV). DCH infection is associated with chronic hepatitis in cats, suggesting its potential as a novel animal model for HBV research. The study also suggests that DCH and HBV may share cell entry molecules, indicating the possibility of interspecies transmission.
ANTIVIRAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Massimo Palatini, Simon Franz Mueller, Kira Alessandra Alicia Theresa Lowjaga, Saskia Noppes, Joerg Alber, Felix Lehmann, Nora Goldmann, Dieter Glebe, Joachim Geyer
Summary: The GXXXG/A motifs in TMD2 and particularly in TMD7 are crucial for proper folding and sorting of NTCP, affecting glycosylation, homodimerization, bile acid transport, and its function as an HBV/HDV receptor.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dariusz Zakrzewicz, Joachim Geyer
Summary: Hepatitis B virus infections are a major public health concern worldwide. A recently discovered high-affinity hepatic host receptor has become a key focus of research for potential therapies. This article presents a newly generated three-dimensional model of the receptor and discusses its role in the entry of HBV into hepatocytes.
Review
Biochemistry & Molecular Biology
Dariusz Zakrzewicz, Joachim Geyer
Summary: Na+/taurocholate cotransporting polypeptide (NTCP) is a transporter involved in the uptake of bile salts and also serves as a receptor for hepatitis B (HBV) and hepatitis D (HDV) viruses. This review highlights recent discoveries on the interactions between NTCP and cofactors relevant to viral entry, and discusses strategies to block these interactions to prevent HBV/HDV infection.
BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yang Liu, Hanying Ruan, Ying Li, Guoliang Sun, Xiao Liu, Wenhui He, Fengfeng Mao, Miaomiao He, Liwei Yan, Guocai Zhong, Huan Yan, Wenhui Li, Zhiyuan Zhang
Summary: The analogue 27A, derived from natural cyclosporine A, shows potent inhibition of HBV/HDV infection by blocking viral engagement to NTCP, without immunosuppressive activity. It serves as a promising lead for novel anti-HDV/HBV agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Vanessa Zhu, Juergen Burhenne, Johanna Weiss, Mathias Haag, Ute Hofmann, Matthias Schwab, Stephan Urban, Gerd Mikus, David Czock, Walter E. Haefeli, Antje Blank
Summary: This study investigated the drug-drug interaction potential and pharmacokinetics of high-dose subcutaneous bulevirtide (5 mg twice daily) with OATP1B1 and CYP3A4. The results showed that high-dose bulevirtide had inhibitory effects on OATP1B-mediated uptake of pravastatin, but the extent of inhibition was not clinically relevant. There were also no clinically relevant changes in CYP3A4 activity. Therefore, it is safe to use OATP1B substrate drugs and CYP3A4 substrate drugs without dose adjustment in patients treated with bulevirtide.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Feiyang Deng, Kyoung Sub Kim, Jiyoung Moon, You Han Bae
Summary: Bile acid-modified nanoparticles can improve oral bioavailability of poorly permeable drugs by interacting with bile acid transporters. This study investigates the transport of glycocholic acid (GCA)-conjugated polystyrene nanoparticles (GCPNs) in Caco-2 cell models and identifies a new pathway correlated with both apical sodium-dependent bile acid transporter (ASBT) and chylomicron pathways. The study also reveals that the higher uptake of GCPNs does not result in higher transcytosis compared to unmodified nanoparticles (CPNs). Pharmacological and genomics analysis indicate that GCA conjugation alters endocytosis mechanisms and downregulates cellular response, leading to higher cellular retention of GCPNs.
Article
Immunology
Zhen Xun, Jinpiao Lin, Qingqing Yu, Can Liu, Jinlan Huang, Hongyan Shang, Jianhui Guo, Yuchen Ye, Wennan Wu, Yongbin Zeng, Songhang Wu, Siyi Xu, Tianbin Chen, Jing Chen, Qishui Ou
Summary: Bile acids (BAs), especially taurocholic acid (TCA), are significantly elevated in HBeAg-positive chronic hepatitis B (CHB) patients and inhibit the response to pegylated interferon-alpha (PegIFN alpha) therapy. These BAs reduce the number, proportion, and effector functions of CD3(+)CD8(+) T cells and natural killer (NK) cells in CHB patients.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
