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An Intracellular Model of Hepatitis B Viral Infection: An In Silico Platform for Comparing Therapeutic Strategies
by Farzad Fatehi
1,2 [OrcID] , Richard J. Bingham
1,2,3 [OrcID] , Eric C. Dykeman
1,2 [OrcID] , Nikesh Patel
4 [OrcID] , Peter G. Stockley
4,* [OrcID] and Reidun Twarock
1,2,3,* [OrcID]
1
York Cross-Disciplinary Centre for Systems Analysis, University of York, York YO10 5GE, UK
2
Department of Mathematics, University of York, York YO10 5DD, UK
3
Department of Biology, University of York, York YO10 5NG, UK
4
Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT UK
*
Authors to whom correspondence should be addressed.
Academic Editors: Richard J. Kuhn, Venigalla B. Rao and Bentley A. Fane
Viruses 2021, 13(1), 11; https://doi.org/10.3390/v13010011
Received: 7 November 2020 / Revised: 17 December 2020 / Accepted: 19 December 2020 / Published: 23 December 2020
(This article belongs to the Special Issue In Memory of Michael Rossmann)
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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.
Keywords: hepatitis B virus; intracellular model; antiviral therapy; packaging signal; virus assembly 作者: StephenW 时间: 2021-1-23 13:18