Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids

The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to d...
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Autor*in:	Paola Spitalieri [verfasserIn] Federica Centofanti [verfasserIn] Michela Murdocca [verfasserIn] Maria Giovanna Scioli [verfasserIn] Andrea Latini [verfasserIn] Silvia Di Cesare [verfasserIn] Gennaro Citro [verfasserIn] Antonio Rossi [verfasserIn] Augusto Orlandi [verfasserIn] Shane Miersch [verfasserIn] Sachdev S. Sidhu [verfasserIn] Pier Paolo Pandolfi [verfasserIn] Annalisa Botta [verfasserIn] Federica Sangiuolo [verfasserIn] Giuseppe Novelli [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	hiPSCs hLORGs SARS-CoV2 pseudovirus neutralizing monoclonal antibody synthetic peptide

Übergeordnetes Werk:	In: Cells - MDPI AG, 2012, 11(2022), 7, p 1235
Übergeordnetes Werk:	volume:11 ; year:2022 ; number:7, p 1235

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cells11071235

Katalog-ID:	DOAJ023939354

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allfields	10.3390/cells11071235 doi (DE-627)DOAJ023939354 (DE-599)DOAJ5feb808c1d324cb795155734be456949 DE-627 ger DE-627 rakwb eng QH573-671 Paola Spitalieri verfasserin aut Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19. hiPSCs hLORGs SARS-CoV2 pseudovirus neutralizing monoclonal antibody synthetic peptide Cytology Federica Centofanti verfasserin aut Michela Murdocca verfasserin aut Maria Giovanna Scioli verfasserin aut Andrea Latini verfasserin aut Silvia Di Cesare verfasserin aut Gennaro Citro verfasserin aut Antonio Rossi verfasserin aut Augusto Orlandi verfasserin aut Shane Miersch verfasserin aut Sachdev S. Sidhu verfasserin aut Pier Paolo Pandolfi verfasserin aut Annalisa Botta verfasserin aut Federica Sangiuolo verfasserin aut Giuseppe Novelli verfasserin aut In Cells MDPI AG, 2012 11(2022), 7, p 1235 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:11 year:2022 number:7, p 1235 https://doi.org/10.3390/cells11071235 kostenfrei https://doaj.org/article/5feb808c1d324cb795155734be456949 kostenfrei https://www.mdpi.com/2073-4409/11/7/1235 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2022 7, p 1235
spelling	10.3390/cells11071235 doi (DE-627)DOAJ023939354 (DE-599)DOAJ5feb808c1d324cb795155734be456949 DE-627 ger DE-627 rakwb eng QH573-671 Paola Spitalieri verfasserin aut Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19. hiPSCs hLORGs SARS-CoV2 pseudovirus neutralizing monoclonal antibody synthetic peptide Cytology Federica Centofanti verfasserin aut Michela Murdocca verfasserin aut Maria Giovanna Scioli verfasserin aut Andrea Latini verfasserin aut Silvia Di Cesare verfasserin aut Gennaro Citro verfasserin aut Antonio Rossi verfasserin aut Augusto Orlandi verfasserin aut Shane Miersch verfasserin aut Sachdev S. Sidhu verfasserin aut Pier Paolo Pandolfi verfasserin aut Annalisa Botta verfasserin aut Federica Sangiuolo verfasserin aut Giuseppe Novelli verfasserin aut In Cells MDPI AG, 2012 11(2022), 7, p 1235 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:11 year:2022 number:7, p 1235 https://doi.org/10.3390/cells11071235 kostenfrei https://doaj.org/article/5feb808c1d324cb795155734be456949 kostenfrei https://www.mdpi.com/2073-4409/11/7/1235 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2022 7, p 1235
allfields_unstemmed	10.3390/cells11071235 doi (DE-627)DOAJ023939354 (DE-599)DOAJ5feb808c1d324cb795155734be456949 DE-627 ger DE-627 rakwb eng QH573-671 Paola Spitalieri verfasserin aut Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19. hiPSCs hLORGs SARS-CoV2 pseudovirus neutralizing monoclonal antibody synthetic peptide Cytology Federica Centofanti verfasserin aut Michela Murdocca verfasserin aut Maria Giovanna Scioli verfasserin aut Andrea Latini verfasserin aut Silvia Di Cesare verfasserin aut Gennaro Citro verfasserin aut Antonio Rossi verfasserin aut Augusto Orlandi verfasserin aut Shane Miersch verfasserin aut Sachdev S. Sidhu verfasserin aut Pier Paolo Pandolfi verfasserin aut Annalisa Botta verfasserin aut Federica Sangiuolo verfasserin aut Giuseppe Novelli verfasserin aut In Cells MDPI AG, 2012 11(2022), 7, p 1235 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:11 year:2022 number:7, p 1235 https://doi.org/10.3390/cells11071235 kostenfrei https://doaj.org/article/5feb808c1d324cb795155734be456949 kostenfrei https://www.mdpi.com/2073-4409/11/7/1235 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2022 7, p 1235
allfieldsGer	10.3390/cells11071235 doi (DE-627)DOAJ023939354 (DE-599)DOAJ5feb808c1d324cb795155734be456949 DE-627 ger DE-627 rakwb eng QH573-671 Paola Spitalieri verfasserin aut Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19. hiPSCs hLORGs SARS-CoV2 pseudovirus neutralizing monoclonal antibody synthetic peptide Cytology Federica Centofanti verfasserin aut Michela Murdocca verfasserin aut Maria Giovanna Scioli verfasserin aut Andrea Latini verfasserin aut Silvia Di Cesare verfasserin aut Gennaro Citro verfasserin aut Antonio Rossi verfasserin aut Augusto Orlandi verfasserin aut Shane Miersch verfasserin aut Sachdev S. Sidhu verfasserin aut Pier Paolo Pandolfi verfasserin aut Annalisa Botta verfasserin aut Federica Sangiuolo verfasserin aut Giuseppe Novelli verfasserin aut In Cells MDPI AG, 2012 11(2022), 7, p 1235 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:11 year:2022 number:7, p 1235 https://doi.org/10.3390/cells11071235 kostenfrei https://doaj.org/article/5feb808c1d324cb795155734be456949 kostenfrei https://www.mdpi.com/2073-4409/11/7/1235 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2022 7, p 1235
allfieldsSound	10.3390/cells11071235 doi (DE-627)DOAJ023939354 (DE-599)DOAJ5feb808c1d324cb795155734be456949 DE-627 ger DE-627 rakwb eng QH573-671 Paola Spitalieri verfasserin aut Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19. hiPSCs hLORGs SARS-CoV2 pseudovirus neutralizing monoclonal antibody synthetic peptide Cytology Federica Centofanti verfasserin aut Michela Murdocca verfasserin aut Maria Giovanna Scioli verfasserin aut Andrea Latini verfasserin aut Silvia Di Cesare verfasserin aut Gennaro Citro verfasserin aut Antonio Rossi verfasserin aut Augusto Orlandi verfasserin aut Shane Miersch verfasserin aut Sachdev S. Sidhu verfasserin aut Pier Paolo Pandolfi verfasserin aut Annalisa Botta verfasserin aut Federica Sangiuolo verfasserin aut Giuseppe Novelli verfasserin aut In Cells MDPI AG, 2012 11(2022), 7, p 1235 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:11 year:2022 number:7, p 1235 https://doi.org/10.3390/cells11071235 kostenfrei https://doaj.org/article/5feb808c1d324cb795155734be456949 kostenfrei https://www.mdpi.com/2073-4409/11/7/1235 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2022 7, p 1235
language	English
source	In Cells 11(2022), 7, p 1235 volume:11 year:2022 number:7, p 1235
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author	Paola Spitalieri
spellingShingle	Paola Spitalieri misc QH573-671 misc hiPSCs misc hLORGs misc SARS-CoV2 pseudovirus misc neutralizing monoclonal antibody misc synthetic peptide misc Cytology Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids
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topic	misc QH573-671 misc hiPSCs misc hLORGs misc SARS-CoV2 pseudovirus misc neutralizing monoclonal antibody misc synthetic peptide misc Cytology
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title_auth	Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids
abstract	The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19.
abstractGer	The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19.
abstract_unstemmed	The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19.
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Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids

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