Literature DB >> 33374798

An Intracellular Model of Hepatitis B Viral Infection: An In Silico Platform for Comparing Therapeutic Strategies.

Farzad Fatehi1,2, Richard J Bingham1,2,3, Eric C Dykeman1,2, Nikesh Patel4, Peter G Stockley4, Reidun Twarock1,2,3.   

Abstract

Hepatitis B virus (HBV) is a major focus of antiviral research worldwide. The International Coalition to Eliminate HBV, together with the World Health Organisation (WHO), have prioritised the search for a cure, with the goal of eliminating deaths from viral hepatitis by 2030. We present here a comprehensive model of intracellular HBV infection dynamics that includes all molecular processes currently targeted by drugs and agrees well with the observed outcomes of several clinical studies. The model reveals previously unsuspected kinetic behaviour in the formation of sub-viral particles, which could lead to a better understanding of the immune responses to infection. It also enables rapid comparative assessment of the impact of different treatment options and their potential synergies as combination therapies. A comparison of available and currently developed treatment options reveals that combinations of multiple capsid assembly inhibitors perform best.

Entities:  

Keywords:  antiviral therapy; hepatitis B virus; intracellular model; packaging signal; virus assembly

Mesh:

Substances:

Year:  2020        PMID: 33374798      PMCID: PMC7823939          DOI: 10.3390/v13010011

Source DB:  PubMed          Journal:  Viruses        ISSN: 1999-4915            Impact factor:   5.818


  63 in total

Review 1.  Hepatitis B cure: From discovery to regulatory approval.

Authors:  Anna S Lok; Fabien Zoulim; Geoffrey Dusheiko; Marc G Ghany
Journal:  J Hepatol       Date:  2017-08-01       Impact factor: 25.083

2.  Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function.

Authors:  Laura Belloni; Teresa Pollicino; Francesca De Nicola; Francesca Guerrieri; Giuseppina Raffa; Maurizio Fanciulli; Giovanni Raimondo; Massimo Levrero
Journal:  Proc Natl Acad Sci U S A       Date:  2009-11-11       Impact factor: 11.205

3.  Dissecting the divergent effects of interferon-alpha on immune cells: time to rethink combination therapy in chronic hepatitis B?

Authors:  Robert Thimme; Maura Dandri
Journal:  J Hepatol       Date:  2012-11-14       Impact factor: 25.083

4.  Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B.

Authors:  Yi-Wen Huang; Kazuaki Chayama; Masataka Tsuge; Shoichi Takahashi; Tsuyoshi Hatakeyama; Hiromi Abe; Jui-Ting Hu; Chun-Jen Liu; Ming-Yang Lai; Ding-Shinn Chen; Sien-Sing Yang; Jia-Horng Kao
Journal:  Antivir Ther       Date:  2010

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

Authors:  Jan Martin Berke; Pascale Dehertogh; Karen Vergauwen; Ellen Van Damme; Wendy Mostmans; Koen Vandyck; Frederik Pauwels
Journal:  Antimicrob Agents Chemother       Date:  2017-07-25       Impact factor: 5.191

6.  In silico single cell dynamics of hepatitis B virus infection and clearance.

Authors:  John M Murray; Ashish Goyal
Journal:  J Theor Biol       Date:  2014-12-02       Impact factor: 2.691

7.  Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA.

Authors:  Julie Lucifora; Yuchen Xia; Florian Reisinger; Ke Zhang; Daniela Stadler; Xiaoming Cheng; Martin F Sprinzl; Herwig Koppensteiner; Zuzanna Makowska; Tassilo Volz; Caroline Remouchamps; Wen-Min Chou; Wolfgang E Thasler; Norbert Hüser; David Durantel; T Jake Liang; Carsten Münk; Markus H Heim; Jeffrey L Browning; Emmanuel Dejardin; Maura Dandri; Michael Schindler; Mathias Heikenwalder; Ulrike Protzer
Journal:  Science       Date:  2014-02-20       Impact factor: 47.728

8.  Binding of p23 and hsp90 during assembly with the progesterone receptor.

Authors:  J L Johnson; D O Toft
Journal:  Mol Endocrinol       Date:  1995-06

Review 9.  A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation-and Beyond?

Authors:  Sabrina Schreiner; Michael Nassal
Journal:  Viruses       Date:  2017-05-22       Impact factor: 5.048

10.  The deubiquitylating enzyme UCHL3 regulates Ku80 retention at sites of DNA damage.

Authors:  Ryotaro Nishi; Paul W G Wijnhoven; Yusuke Kimura; Misaki Matsui; Rebecca Konietzny; Qian Wu; Keisuke Nakamura; Tom L Blundell; Benedikt M Kessler
Journal:  Sci Rep       Date:  2018-12-17       Impact factor: 4.379

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  3 in total

1.  In vitro functional analysis of gRNA sites regulating assembly of hepatitis B virus.

Authors:  Nikesh Patel; Sam Clark; Eva U Weiß; Carlos P Mata; Jen Bohon; Erik R Farquhar; Daniel P Maskell; Neil A Ranson; Reidun Twarock; Peter G Stockley
Journal:  Commun Biol       Date:  2021-12-16

2.  Comparing antiviral strategies against COVID-19 via multiscale within-host modelling.

Authors:  F Fatehi; R J Bingham; E C Dykeman; P G Stockley; R Twarock
Journal:  R Soc Open Sci       Date:  2021-08-11       Impact factor: 2.963

3.  Therapeutic interfering particles exploiting viral replication and assembly mechanisms show promising performance: a modelling study.

Authors:  Farzad Fatehi; Richard J Bingham; Pierre-Philippe Dechant; Peter G Stockley; Reidun Twarock
Journal:  Sci Rep       Date:  2021-12-13       Impact factor: 4.379

  3 in total

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