A Prototype QSP Model of the Immune Response to SARS-CoV-2 for Community Development.
A Prototype QSP Model of the Immune Response to SARS-CoV-2 for Community Development.
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DOI：
10.1002/psp4.12574
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Allen R
中科院分区：
文献类型：
--
作者：
Dai W;Rao R;Sher A;Tania N;Musante CJ;Allen R
严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）大流行需要快速开发针对2019年威胁生命的冠状病毒病（COVID-19）患者的有效治疗方法。定量系统药理学（QSP）模型是病理生理学的数学表示，用于模拟和预测现有或假定的治疗效果。包括QSP在内的基于模型的方法的应用加速了一些新疗法的发展。然而，疾病规模机制模型的开发可能是一个缓慢的过程，通常需要数年时间才能验证并被认为是成熟的。此外，新出现的数据可能会使任何快速启动方案模型很快过时。我们提出了一个原型QSP模型，以促进科学界的进一步发展。该模型解释了病毒动力学、主要宿主免疫应答介质与组织损伤和再生之间的相互作用。免疫应答由调节病毒清除和细胞损伤的先天性和适应性免疫过程的病毒激活决定。原型模型捕获了感染后的两个生理相关结果：适当防御病毒的“健康”免疫反应，以及急性呼吸窘迫综合征特征的不受控制的肺泡炎症反应。我们的目标是通过鼓励社区使用、测试和改进这个原型模型来显著缩短典型的QSP模型开发和验证的时间轴。我们期望该模型将以开放科学的方式进一步发展（即，通过在一个开放论坛上对一个经过验证的定量平台的多个贡献），最终目标是为患者提供信息并加速开发安全有效的治疗方案。
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic requires the rapid development of efficacious treatments for patients with life‐threatening coronavirus disease 2019 (COVID‐19). Quantitative systems pharmacology (QSP) models are mathematical representations of pathophysiology for simulating and predicting the effects of existing or putative therapies. The application of model‐based approaches, including QSP, have accelerated the development of some novel therapeutics. Nevertheless, the development of disease‐scale mechanistic models can be a slow process, often taking years to be validated and considered mature. Furthermore, emerging data may make any QSP model quickly obsolete. We present a prototype QSP model to facilitate further development by the scientific community. The model accounts for the interactions between viral dynamics, the major host immune response mediators and tissue damage and regeneration. The immune response is determined by viral activation of innate and adaptive immune processes that regulate viral clearance and cell damage. The prototype model captures two physiologically relevant outcomes following infection: a “healthy” immune response that appropriately defends against the virus, and an uncontrolled alveolar inflammatory response that is characteristic of acute respiratory distress syndrome. We aim to significantly shorten the typical QSP model development and validation timeline by encouraging community use, testing, and refinement of this prototype model. It is our expectation that the model will be further advanced in an open science approach (i.e., by multiple contributions toward a validated quantitative platform in an open forum), with the ultimate goal of informing and accelerating the development of safe and effective treatment options for patients.
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影响因子：
3.7
作者：
Dobrovolny HM;Reddy MB;Kamal MA;Rayner CR;Beauchemin CA
通讯作者：
Beauchemin CA
影响因子：
158.5
作者：
Li, Qun;Guan, Xuhua;Feng, Zijian
通讯作者：
Feng, Zijian
DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
4.6
作者：
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通讯作者：
Smith, Maxwell Lawrence
影响因子：
5.1
作者：
Fernandez-Botran, Rafael;Uriarte, Silvia M.;Bordon, Jose
通讯作者：
Bordon, Jose