key: cord-0774722-hse0bui5
authors: Wang, Jianhai; Li, Xue; Wang, An; Zhao, Fuxiaonan; Wu, Qi; Li, Li; Yu, Hongzhi; Wu, Junping; Chen, Huaiyong
title: Organoid technology demonstrates effects of potential drugs for COVID‐19 on the lung regeneration
date: 2020-10-19
journal: Cell Prolif
DOI: 10.1111/cpr.12928
sha: 8ba118b7106dfc5babcae3456a462d8e87e0f533
doc_id: 774722
cord_uid: hse0bui5

nan

To the Editor, Upon entry into the lungs, SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor to facilitate viral entry into the epithelial cells that cover the airways and the alveolar gas-exchanging space, leading to extensive epithelial injury, which contributes to local inflammatory storm and a series of respiratory syndromes. Mouse club and AT2 cells were sorted and cultured in a 3D organoid-based system as previously described ( Figure 1A and B). 6 Chloroquine was shown to inhibit the production of SARS-CoV-2 (EC 50 = 1.13 μmol/L). 7 Chloroquine did not affect colony-forming ef- 

We are grateful to Dr Zichuan Liu at Tianjin University for critical review and constructive advice. This study was supported by the National Natural Science Foundation of China (81773394, 81970001 and 82070001) and the Natural Science Foundation of Tianjin (18ZXDBSY00150 and 19JCZDJC33600).

The authors have no financial conflicts of interest. F I G U R E 1 Drug candidates being tested against SARS-CoV-2 have various distinct effects on the viability, proliferation and differentiation of mouse progenitor cells. A, Club and AT2 cells were segregated from mouse lung epithelial cells by fluorescence-activated cell sorting. B, Club cells and AT2 cells were cultured in a organoid platform, and organoids derived from club cells (day 7 after seeding) or from AT2 cells (day 10 after seeding) were imaged. C, G, Colony-forming efficiency (CFE) of club cells or AT2 cells in the absence or presence of indicated potential drugs for COVID-19 were calculated. D, H, Size of organoids derived from club cells or AT2 cells was quantified. E-F, Foxj1 and Foxa3 mRNA expression was measured in club organoid cultures. I, T1α mRNA expression was measured in AT2 organoid cultures. Doses of drugs: chloroquine (0, 1, 10 μmol/L); remdesivir (0, 1, 10 μmol/L); lopinavir (0, 10, 50 μmol/L); ritonavir (0, 10, 50 μmol/L); umifenovir (0, 1, 10 μmol/L); ribavirin (0, 100, 500 μmol/L); and favipiravir (0, 50, 500 μmol/L). *P ˂ .05, **P ˂ .01; all data shown are means ± SD. Scale bar, 500 μm

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