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Abstract: There is a pressing need for efective therapeutics for coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The process of drug development is a costly and meticulously paced process, where progress is often hindered by the failure of initially promising leads. To aid this challenge, in vitro human microphysiological systems need to be refned and adapted for mechanistic studies and drug screening, thereby saving valuable time and resources during a pandemic crisis. The SARS-CoV-2 virus attacks the lung, an organ where the unique three-dimensional (3D) structure of its functional units is critical for proper respiratory function. The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between diferent cell types. Current model systems include Transwell, organoid and organ-on-a-chip or microphysiological systems (MPSs). We review models that have direct relevance toward modeling the pathology of COVID-19, including the processes of infammation, edema, coagulation, as well as lung immune function. We also consider the practical issues that may infuence the design and fabrication of MPS. The role of lung MPS is addressed in the context of multi-organ models, and it is discussed how high-throughput screening and artifcial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.

UCLA Argus M. Sun等 | 肺微生理系统在COVID-19建模和药物发现中的应用

本综述论文聚焦肺微生理系统在新型冠状病毒病理模型建立与药物研发中的应用。我们迫切需要有效的治疗方法来应对新型冠状病毒病（COVID-19），这是由严重急性呼吸综合征冠状病毒（SARS-CoV-2）引起的呼吸道疾病。药物开发是一个昂贵且细致的过程，其进展往往受限于寻找最初的相关线索。为了帮助解决这一问题，我们需要对体外人体微生理系统进行改进和调整，以进行机理研究和药物筛选，从而在疫情期间节省宝贵的时间和资源。SARS-CoV-2病毒攻击肺部，这一以其功能单元的独特三维结构对正常呼吸功能至关重要的器官。体外肺模型基本上概括了不同的组织结构以及不同细胞类型之间的动力学、机械和生物相互作用。目前的模型系统包括Transwell迁移侵袭实验，类器官和器官芯片或微生理系统（MPS）。本文综述了与COVID-19病理学建模直接相关的模型，包括炎症、水肿、凝血以及肺免疫功能的过程。我们还考虑了可能影响微生理系统设计和制造的实际问题。阐述了多器官模型背景下肺微生理系统的作用，并讨论了如何将高通量筛查和人工智能与肺微生理系统相结合，以加速COVID-19和其他传染病的药物开发。