York Cross-Disciplinary Centre for Systems Analysis, University of York, York YO10 5GE, UK.
Department of Mathematics, University of York, York YO10 5DD, UK.
Viruses. 2020 Dec 23;13(1):11. doi: 10.3390/v13010011.
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.
乙型肝炎病毒(HBV)是全球抗病毒研究的重点。国际消除乙型肝炎病毒联盟与世界卫生组织(WHO)一起,将寻找治愈方法作为优先事项,目标是到 2030 年消除因病毒性肝炎导致的死亡。我们在此提出了一个包含所有目前药物靶向分子过程的乙型肝炎病毒感染动力学综合模型,该模型与多项临床研究的观察结果吻合较好。该模型揭示了亚病毒颗粒形成过程中以前未被察觉的动力学行为,这可能有助于更好地理解对感染的免疫反应。它还可以快速比较不同治疗方案的影响及其作为联合疗法的潜在协同作用。对现有和正在开发的治疗方案的比较表明,多种衣壳组装抑制剂的联合使用效果最佳。