aso52v2h

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?: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 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.
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?:creator	<https://research.tib.eu/covid-19/entity/Han%2C_Y.%3B_Duan%2C_X.%3B_Yang%2C_L.%3B_Nilsson-Payant%2C_B._E.%3B_Wang%2C_P.%3B_Duan%2C_F.%3B_Tang%2C_X.%3B_Yaron%2C_T._M.%3B_Zhang%2C_T.%3B_Uhl%2C_S.%3B_Bram%2C_Y.%3B_Richardson%2C_C.%3B_Zhu%2C_J.%3B_Zhao%2C_Z.%3B_Redmond%2C_D.%3B_Houghton%2C_S.%3B_Nguyen%2C_D._T.%3B_Xu%2C_D.%3B_Wang%2C_X.%3B_Jessurun%2C_J.%3B_Borczuk%2C_A.%3B_Huang%2C_Y.%3B_Johnson%2C_J._L.%3B_Liu%2C_Y.%3B_Xiang%2C_J.%3B_Wang%2C_H.%3B_Cantley%2C_L._C.%3B_tenOever%2C_B._R.%3B_Ho%2C_D._D.%3B_Pan%2C_F._C.%3B_Evans%2C_T.%3B_Chen%2C_H._J.%3B_Schwartz%2C_R._E.%3B_Chen%2C_S.> <https://research.tib.eu/covid-19/entity/Han%2C_Yuling%3B_Duan%2C_Xiaohua%3B_Yang%2C_Liuliu%3B_Nilsson-Payant%2C_Benjamin_E%3B_Wang%2C_Pengfei%3B_Duan%2C_Fuyu%3B_Tang%2C_Xuming%3B_Yaron%2C_Tomer_M%3B_Zhang%2C_Tuo%3B_Uhl%2C_Skyler%3B_Bram%2C_Yaron%3B_Richardson%2C_Chanel%3B_Zhu%2C_Jiajun%3B_Zhao%2C_Zeping%3B_Redmond%2C_David%3B_Houghton%2C_Sean%3B_Nguyen%2C_Duc-Huy_T%3B_Xu%2C_Dong%3B_Wang%2C_Xing%3B_Jessurun%2C_Jose%3B_Borczuk%2C_Alain%3B_Huang%2C_Yaoxing%3B_Johnson%2C_Jared_L%3B_Liu%2C_Yuru%3B_Xiang%2C_Jenny%3B_Wang%2C_Hui%3B_Cantley%2C_Lewis_C%3B_tenOever%2C_Benjamin_R%3B_Ho%2C_David_D%3B_Pan%2C_Fong_Cheng%3B_Evans%2C_Todd%3B_Chen%2C_Huanhuan_Joyce%3B_Schwartz%2C_Robert_E%3B_Chen%2C_Shuibing>
?:journal	Nature Nature_(Lond.)
?:license	unk
?:publication_isRelatedTo_Disease	<https://research.tib.eu/covid-19/entity/COVID-19>
is ?:relation_isRelatedTo_publication of	<https://research.tib.eu/covid-19/entity/aso52v2h_HAS_C0013227_DISRUPTS_C5203670> <https://research.tib.eu/covid-19/entity/aso52v2h_HAS_C0682610_PRODUCES_C1422064>
?:source	WHO
?:title	Identification of SARS-CoV-2 inhibitors using lung and colonic organoids
?:type	<https://research.tib.eu/covid-19/vocab/Publication>
?:who_covidence_id	#1065893 #894402
?:year	2020 2021

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?: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
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.

is ?:annotates of