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临床相关细胞培养模型及其在 SARS-CoV-2 的分离、发病机制、疫苗开发、新药再利用和筛选中的意义:系统评价。

Clinically relevant cell culture models and their significance in isolation, pathogenesis, vaccine development, repurposing and screening of new drugs for SARS-CoV-2: a systematic review.

机构信息

Department of Pharmacology, PGIMER, Chandigarh, India.

Ophthalmology, GMCH-32, Chandigarh, India.

出版信息

Tissue Cell. 2021 Jun;70:101497. doi: 10.1016/j.tice.2021.101497. Epub 2021 Jan 26.

DOI:10.1016/j.tice.2021.101497
PMID:33550034
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7836970/
Abstract

BACKGROUND

In-Vitro/Cellular evidence is the backbone and vital proof of concept during the development of novel therapeutics as well as drugs repurposing against COVID-19. Choosing an ideal in-vitro model is vital as the virus entry is through ACE2, CD147, and TMPRSS2 dependant and very specific. In this regard, this is the first systematic review addressing the importance of specific cell lines used as potential in-vitro models in the isolation, pathogenesis, and therapeutics for SARS-COV-2.

METHODS

We searched 17 literature databases with appropriate keywords, and identified 1173 non-duplicate studies. In the present study, 71 articles are included after a careful, thorough screening of the titles and their abstracts for possible inclusion using predefined inclusion/exclusion criteria (PRISMA Guidelines).

RESULTS

In the current study, we compiled cell culture-based studies for SARS-CoV-2 and found the best compatible In-Vitro models for SARS-CoV-2 (Vero, VeroE6, HEK293 as well as its variants, Huh-7, Calu-3 2B4, and Caco2). Among other essential cell lines used include LLC-MK2, MDCKII, BHK-21, HepG2, A549,T cell leukemia (MT-2), stems cells based cell line DYR0100for differentiation assays, and embryo-specific NIH3T3 cell line for vaccine production.

CONCLUSION

The Present study provides a detailed summary of all the drugs/compounds screened for drug repurposing and discovery purpose using the in-vitro models for SARS-CoV-2 along with isolation, pathogenesis and vaccine production. This study also suggests that after careful evaluation of all the cell line based studies, Kidney cells (VeroE6, HEK293 along with their clones), liver Huh-7cells, respiratory Calu-3 cells, and intestinal Caco-2 are the most widely used in-vitro models for SARS-CoV-2.

摘要

背景

在针对 COVID-19 的新型治疗药物和药物再利用的开发过程中,体外/细胞证据是基础和重要的概念验证。选择理想的体外模型至关重要,因为病毒的进入是通过 ACE2、CD147 和 TMPRSS2 依赖且非常特异的。在这方面,这是第一项针对 SARS-CoV-2 分离、发病机制和治疗中使用的潜在体外模型的特定细胞系的重要性进行的系统评价。

方法

我们使用适当的关键词搜索了 17 个文献数据库,并确定了 1173 篇非重复研究。在本研究中,经过仔细、彻底的标题筛选和摘要筛选,使用预定义的纳入/排除标准(PRISMA 指南),确定了 71 篇文章。

结果

在本研究中,我们编译了基于细胞培养的 SARS-CoV-2 研究,并找到了最适合 SARS-CoV-2 的体外模型(Vero、VeroE6、HEK293 及其变体、Huh-7、Calu-3、2B4 和 Caco2)。其他重要的细胞系包括 LLC-MK2、MDCKII、BHK-21、HepG2、A549、T 细胞白血病(MT-2)、用于分化试验的基于干细胞的 DYR0100 细胞系和用于疫苗生产的胚胎特异性 NIH3T3 细胞系。

结论

本研究提供了使用 SARS-CoV-2 体外模型进行药物再利用和发现筛选的所有药物/化合物的详细总结,以及分离、发病机制和疫苗生产。本研究还表明,在仔细评估所有基于细胞系的研究后,肾脏细胞(VeroE6、HEK293 及其克隆)、肝脏 Huh-7 细胞、呼吸道 Calu-3 细胞和肠道 Caco-2 是 SARS-CoV-2 最广泛使用的体外模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0a2/7836970/93250c1f2fcc/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0a2/7836970/93250c1f2fcc/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0a2/7836970/93250c1f2fcc/gr1_lrg.jpg

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