scholarly journals Naturally derived anti-hepatitis B virus agents and their mechanism of action

2016 ◽  
Vol 22 (1) ◽  
pp. 188 ◽  
Author(s):  
Yi-Hang Wu
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mechanism Of Action ◽  
B Virus

scholarly journals Capsid Assembly Modulators Have a Dual Mechanism of Action in Primary Human Hepatocytes Infected with Hepatitis B Virus

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Jan Martin Berke ◽  
Pascale Dehertogh ◽  
Karen Vergauwen ◽  
Ellen Van Damme ◽  
Wendy Mostmans ◽  
...  
Keyword(s):  
Life Cycle ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mechanism Of Action ◽  
Viral Life Cycle ◽  
Human Hepatocytes ◽  
Capsid Assembly ◽  
B Virus ◽  
Dual Mechanism ◽  
Dose Dependent

ABSTRACT Hepatitis B virus (HBV) capsid assembly is a critical step in the propagation of the virus and is mediated by the core protein. Due to its multiple functions in the viral life cycle, core became an attractive target for new antiviral therapies. Capsid assembly modulators (CAMs) accelerate the kinetics of capsid assembly and prevent encapsidation of the polymerase-pregenomic RNA (Pol-pgRNA) complex, thereby blocking viral replication. CAM JNJ-632 is a novel and potent inhibitor of HBV replication in vitro across genotypes A to D. It induces the formation of morphologically intact viral capsids, as demonstrated by size exclusion chromatography and electron microscopy studies. Antiviral profiling in primary human hepatocytes revealed that CAMs prevented formation of covalently closed circular DNA in a dose-dependent fashion when the compound was added together with the viral inoculum, whereas nucleos(t)ide analogues (NAs) did not. This protective effect translated into a dose-dependent reduction of intracellular HBV RNA levels as well as reduced HBe/cAg and HBsAg levels in the cell culture supernatant. The same observation was made with another CAM (BAY41-4109), suggesting that mechanistic rather than compound-specific effects play a role. Our data show that CAMs have a dual mechanism of action, inhibiting early and late steps of the viral life cycle. These effects clearly differentiate CAMs from NAs and may translate into higher functional cure rates in a clinical setting when given alone or in combination with the current standard of care.

Discovery of RG7834: The First-in-Class Selective and Orally Available Small Molecule Hepatitis B Virus Expression Inhibitor with Novel Mechanism of Action

2018 ◽  
Vol 61 (23) ◽  
pp. 10619-10634 ◽  
Author(s):  
Xingchun Han ◽  
Chengang Zhou ◽  
Min Jiang ◽  
Yongguang Wang ◽  
Jianhua Wang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Small Molecule ◽  
Mechanism Of Action ◽  
B Virus ◽  
Virus Expression

Mechanism of action of vaccine therapy in murine hepatitis B virus carriers: vaccine-induced activation of antigen presenting dendritic cells

1999 ◽  
Vol 30 (5) ◽  
pp. 755-764 ◽  
Author(s):  
Sk.Md.Fazle Akbar ◽  
Masanori Abe ◽  
Toshikazu Masumoto ◽  
Norio Horiike ◽  
Morikazu Onji
Keyword(s):  
Dendritic Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mechanism Of Action ◽  
Vaccine Therapy ◽  
B Virus ◽  
Antigen Presenting

scholarly journals Preclinical Profile and Characterization of the Hepatitis B Virus Core Protein Inhibitor ABI-H0731

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Qi Huang ◽  
Dawei Cai ◽  
Ran Yan ◽  
Lichun Li ◽  
Yuhua Zong ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Dna Replication ◽  
Hepatitis B ◽  
Mechanism Of Action ◽  
De Novo ◽  
Core Protein ◽  
Protein Inhibitor ◽  
Circular Dna ◽  
B Virus

ABSTRACT ABI-H0731, a first-generation hepatitis B virus (HBV) core protein inhibitor, has demonstrated effective antiviral activity in chronic hepatitis B (CHB) patients in a phase 1b clinical trial and is currently being further evaluated in phase 2 clinical trials. Here, we report the preclinical profile of ABI-H0731. In in vitro cell culture systems (HepG2-derived cell lines HepAD38 and HepG2-NTCP and primary human hepatocytes [PHHs]), ABI-H0731 exhibited selective inhibition of HBV DNA replication (50% effective concentration [EC50] from 173 nM to 307 nM). Most importantly, ABI-H0731 suppressed covalently closed circular DNA (cccDNA) formation in two de novo infection models with EC50s from 1.84 μM to 7.3 μM. Mechanism-of-action studies indicated that ABI-H0731 is a direct-acting antiviral that targets HBV core protein, preventing HBV pregenomic RNA (pgRNA) encapsidation and subsequent DNA replication. The combination of ABI-H0731 with entecavir appears to decrease viral DNA faster and deeper than nucleoside/nucleotide analogue (NrtI) therapy alone. In addition, ABI-H0731 disrupts incoming nucleocapsids, causing the premature release of relaxed circular DNA (rcDNA) before delivery to the nucleus, and thus prevents new cccDNA formation. ABI-H0731 exhibits pangenotypic activity and is additive to moderately synergistic when combined with an NrtI. In addition to its potency and novel mechanism of action, ABI-H0731 possesses drug-like properties and a preclinical pharmacokinetic profile supportive of once-daily dosing in patients with CHB. Taken together, these data support the ongoing clinical development of ABI-H0731 as a treatment for HBV.

Precore hepatitis B virus carrying lamivudine resistant mutations are not associated with decreassed replication fitness and are sensitive to adefovir

2001 ◽  
Vol 120 (5) ◽  
pp. A64-A64
Author(s):  
R CHEN ◽  
P DESMOND ◽  
W DELANEY ◽  
D COLLEDGE ◽  
R EDWARDS ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Virus ◽  
Replication Fitness
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