Details

Autor(en) / Beteiligte

• Han, Yuling
• Duan, Xiaohua
• Yang, Liuliu
• Nilsson-Payant, Benjamin E
• Wang, Pengfei
• Duan, Fuyu
• Tang, Xuming
• Yaron, Tomer M
• Zhang, Tuo
• Uhl, Skyler
• Bram, Yaron
• Richardson, Chanel
• Zhu, Jiajun
• Zhao, Zeping
• Redmond, David
• Houghton, Sean
• Nguyen, Duc-Huy T
• Xu, Dong
• Wang, Xing
• Jessurun, Jose
• Borczuk, Alain
• Huang, Yaoxing
• Johnson, Jared L
• Liu, Yuru
• Xiang, Jenny
• Wang, Hui
• Cantley, Lewis C
• tenOever, Benjamin R
• Ho, David D
• Pan, Fong Cheng
• Evans, Todd
• Chen, Huanhuan Joyce
• Schwartz, Robert E
• Chen, Shuibing

Titel

Identification of SARS-CoV-2 inhibitors using lung and colonic organoids

Ist Teil von

• Nature (London), 2021-01, Vol.589 (7841), p.270-275

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• There is an urgent need to create novel models using human disease-relevant cells to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biology and to facilitate drug screening. Here, as SARS-CoV-2 primarily infects the respiratory tract, we developed a lung organoid model using human pluripotent stem cells (hPSC-LOs). The hPSC-LOs (particularly alveolar type-II-like cells) are permissive to SARS-CoV-2 infection, and showed robust induction of chemokines following SARS-CoV-2 infection, similar to what is seen in patients with COVID-19. Nearly 25% of these patients also have gastrointestinal manifestations, which are associated with worse COVID-19 outcomes . We therefore also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. We found that multiple colonic cell types, especially enterocytes, express ACE2 and are permissive to SARS-CoV-2 infection. Using hPSC-LOs, we performed a high-throughput screen of drugs approved by the FDA (US Food and Drug Administration) and identified entry inhibitors of SARS-CoV-2, including imatinib, mycophenolic acid and quinacrine dihydrochloride. Treatment at physiologically relevant levels of these drugs significantly inhibited SARS-CoV-2 infection of both hPSC-LOs and hPSC-COs. Together, these data demonstrate that hPSC-LOs and hPSC-COs infected by SARS-CoV-2 can serve as disease models to study SARS-CoV-2 infection and provide a valuable resource for drug screening to identify candidate COVID-19 therapeutics.