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用于抗SARS-CoV-2药物筛选的条件重编程人角膜缘上皮细胞模型

Conditional reprogrammed human limbal epithelial cell model for anti-SARS-CoV-2 drug screening.

作者信息

Xiao Yu, Wang Ling, Li Shi-Xu, Fang Shi-Song, Luo Fan, Chen Shu-Liang, Zou Xuan, Ye Lin, Hou Wei

机构信息

Shenzhen Research Institute, Wuhan University, Shenzhen 518057, Guangdong Province, China.

Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, China.

出版信息

Heliyon. 2024 Apr 23;10(9):e30044. doi: 10.1016/j.heliyon.2024.e30044. eCollection 2024 May 15.

DOI:10.1016/j.heliyon.2024.e30044
PMID:38698981
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11064458/
Abstract

To minimize the global pandemic COVID-19 spread, understanding the possible transmission routes of SARS-CoV-2 and discovery of novel antiviral drugs are necessary. We describe here that the virus can infect ocular surface limbal epithelial, but not other regions. Limbal supports wild type and mutant SARS-CoV-2 entry and replication depending on ACE2, TMPRSS2 and possibly other receptors, resulting in slight CPE and arising IL-6 secretion, which symbolizes conjunctivitis in clinical symptoms. With this limbal model, we have screened two natural product libraries and discovered several unreported drugs. Our data reveal important commonalities between COVID-19 and ocular infection with SARS-CoV-2, and establish an ideal cell model for drug screening and mechanism research.

摘要

为尽量减少全球新冠疫情的传播，了解严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的可能传播途径并发现新型抗病毒药物很有必要。我们在此描述该病毒可感染眼表角膜缘上皮细胞，但不感染其他区域。角膜缘支持野生型和突变型SARS-CoV-2的进入和复制，这取决于血管紧张素转换酶2（ACE2）、跨膜丝氨酸蛋白酶2（TMPRSS2）以及可能的其他受体，导致轻微的细胞病变效应并引起白细胞介素-6分泌，这在临床症状上表现为结膜炎。利用这个角膜缘模型，我们筛选了两个天然产物文库并发现了几种未报道的药物。我们的数据揭示了新冠病毒病与SARS-CoV-2眼部感染之间的重要共性，并建立了一个用于药物筛选和机制研究的理想细胞模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/d3cbdb324e24/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/10b974bc450a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/0d5d37deadaa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/63aadfd580f9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/3c4d5ee3e0dc/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/9fcc533d762a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/e70a98675edd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/ee060f871e7f/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/31da3fe137cf/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/b50cc1e2021a/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/d3cbdb324e24/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/10b974bc450a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/0d5d37deadaa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/63aadfd580f9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/3c4d5ee3e0dc/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/9fcc533d762a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/e70a98675edd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/ee060f871e7f/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/31da3fe137cf/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/b50cc1e2021a/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11064458/d3cbdb324e24/mmcfigs4.jpg

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