@article{1826,
  keywords = {Animals, Antiviral Agents, COVID-19, COVID-19 Drug Treatment, Colon, Drug Approval, Drug Evaluation, Preclinical, Female, Heterografts, Humans, In Vitro Techniques, Lung, Male, Mice, organoids, SARS-CoV-2, United States, United States Food and Drug Administration, Viral Tropism, Virus Internalization},
  author = {Yuling Han and Xiaohua Duan and Liuliu Yang and Benjamin E. Nilsson-Payant and Pengfei Wang and Fuyu Duan and Xuming Tang and Tomer M. Yaron and Tuo Zhang and Skyler Uhl and Yaron Bram and Chanel Richardson and Jiajun Zhu and Zeping Zhao and David Redmond and Sean Houghton and Duc-Huy T. Nguyen and Dong Xu and Xing Wang and Jose Jessurun and Alain Borczuk and Yaoxing Huang and Jared L. Johnson and Yuru Liu and Jenny Xiang and Hui Wang and Lewis C. Cantley and Benjamin R. tenOever and David D. Ho and Fong Cheng Pan and Todd Evans and Huanhuan Joyce Chen and Robert E. Schwartz and Shuibing Chen},
  title = {Identification of SARS-CoV-2 inhibitors using lung and colonic organoids},
  abstract = {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 outcomes1. 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.},
  year = {2021},
  journal = {Nature},
  volume = {589},
  pages = {270-275},
  month = {2021-01},
  issn = {1476-4687},
  doi = {10.1038/s41586-020-2901-9},
  language = {eng},
}