乙型肝炎病毒感染的细胞内模型：比较治疗策略的计算机平

StephenW

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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

StephenW

乙型肝炎病毒感染的细胞内模型：比较治疗策略的计算机平台。
通过Farzad Fatehi
1,2 [OrcID]，Richard J. Bingham
1,2,3 [OrcID]，埃里克·戴克曼
1,2 [OrcID]，耐克（Nikesh Patel）
4 [OrcID]，彼得·G·斯托克利
4，* [OrcID]和Reidun Twarock
1,2,3，* [OrcID]
1个
约克大学约克系统分析跨学科中心，约克YO10 5GE，英国
2
约克大学数学系，约克YO10 5DD，英国
3
英国约克大学生物系YO10 5NG，英国
4
利兹大学阿斯特伯里结构分子生物学中心，英国利兹LS2 9JT
*
应与之联系的作者。
学术编辑：Richard J. Kuhn，Venigalla B. Rao和Bentley A. Fane
病毒2021，13（1），11; https://doi.org/10.3390/v13010011
收到：2020年11月7日/修订版：2020年12月17日/接受：2020年12月19日/发布：2020年12月23日
（本文属于《纪念迈克尔·罗斯曼的特刊》）
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引文出口
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乙型肝炎病毒（HBV）是全球抗病毒研究的主要重点。国际消除HBV联盟与世界卫生组织（WHO）一起优先寻求治疗方法，目标是到2030年消除病毒性肝炎死亡。目前所有药物靶向的分子过程均与数项临床研究的观察结果相吻合。该模型揭示了亚病毒颗粒形成过程中先前未曾预料到的动力学行为，这可能导致人们更好地理解对感染的免疫反应。它还可以快速比较评估不同治疗方案的影响及其作为联合疗法的潜在协同作用。比较可用的治疗方案和当前开发的治疗方案可发现，多种衣壳装配抑制剂的组合效果最佳。
关键词：乙型肝炎病毒；细胞内模型抗病毒治疗；包装信号；病毒组装

StephenW

https://www.mdpi.com/1999-4915/13/1/11/htm