比较体外和体内模型作为COVID-19药物临床前研究的一部分

Poppy Bradley
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摘要

SARS-CoV-2 (COVID-19的病原)的出现要求有必要开发强大的体外和体内模型,作为新疗法和治疗方法临床前测试的一部分。用于研究SARS-CoV-2的体外研究包括使用细胞系和类器官,这些细胞系和类器官具有使用ACE2受体进行操纵以保持高病毒载量的优势。然而,尽管一些药物在体外研究中有类似的数据读数,如瑞德西韦和羟氯喹的相互冲突的批准所证明的那样,这些研究本身并不能完全反映人体组织的生理学。因此,研究人员利用小型和大型哺乳动物进行体内研究,以更好地了解COVID-19如何在体内系统地相互作用。本文比较了不同的COVID-19发病机制模型,并考虑了它们在开发候选药物或测试现有药物方面的优势和局限性。虽然体外和体内方法都有各自的优点和缺点,但它们共同允许通过临床试验探索治疗方法并降低临床失败的风险。正如2019冠状病毒病大流行期间所强调的那样,反思和有意义的模式对于应对近代史上最大的医疗保健挑战之一至关重要。
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Comparing In Vitro and In Vivo Models as Part of Pre-Clinical Studies for COVID-19 Medicines
The emergence of SARS-CoV-2 (the aetiological agent of COVID-19) has called for the need to develop robust in vitro and in vivo models as part of the pre-clinical testing of novel therapeutics and treatments. In vitro studies used to study SARS-CoV-2 have included use of cell lines and organoids, which have the advantage of being manipulated to retain high viral loads using the ACE2 receptor. However, despite some drugs having similar data readouts during in vitro studies, as demonstrated by the conflicting approvals of remdesivir and hydroxychloroquine, these studies alone are not entirely reflective of the physiology of human tissue. Therefore, in vivo studies have been used small and large mammals to better understand how COVID-19 interact systematically in the body. This review compares different models of COVID-19 pathogenesis, considering their advantages and limitations to developing candidate drugs or testing existing drugs. Whilst both in vitro and in vivo methods have their advantages and disadvantages, together they allow for the expedition of therapies through clinical trials and reduce the risk of clinical failure. As highlighted during the COVID-19 pandemic, reflective and meaningful models have been crucial in tackling one of the biggest healthcare challenges in recent history.
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