MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2

Abstract Although the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a worldwide pandemic, there are currently no virus-specific drugs that are fully effective against SARS-CoV-2. Only a limited number of human-derived cells are capable of supporting SARS-CoV-...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kentaro Uemura, Michihito Sasaki, Takao Sanaki, Shinsuke Toba, Yoshimasa Takahashi, Yasuko Orba, William W. Hall, Katsumi Maenaka, Hirofumi Sawa, Akihiko Sato
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b7cd11ffa764b428313e3718883b4d1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2b7cd11ffa764b428313e3718883b4d1
record_format	dspace
spelling	oai:doaj.org-article:2b7cd11ffa764b428313e3718883b4d12021-12-02T15:54:09ZMRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-210.1038/s41598-021-84882-72045-2322https://doaj.org/article/2b7cd11ffa764b428313e3718883b4d12021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84882-7https://doaj.org/toc/2045-2322Abstract Although the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a worldwide pandemic, there are currently no virus-specific drugs that are fully effective against SARS-CoV-2. Only a limited number of human-derived cells are capable of supporting SARS-CoV-2 replication and the infectivity of SARS-CoV-2 in these cells remains poor. In contrast, monkey-derived Vero cells are highly susceptibility to infection with SARS-CoV-2, although they are not suitable for the study of antiviral effects by small molecules due to their limited capacity to metabolize drugs compared to human-derived cells. In this study, our goal was to generate a virus-susceptible human cell line that would be useful for the identification and testing of candidate drugs. Towards this end, we stably transfected human lung-derived MRC5 cells with a lentiviral vector encoding angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2. Our results revealed that SARS-CoV-2 replicates efficiently in MRC5/ACE2 cells. Furthermore, viral RNA replication and progeny virus production were significantly reduced in response to administration of the replication inhibitor, remdesivir, in MRC5/ACE2 cells compared with Vero cells. We conclude that the MRC5/ACE2 cells will be important in developing specific anti-viral therapeutics and will assist in vaccine development to combat SARS-CoV-2 infections.Kentaro UemuraMichihito SasakiTakao SanakiShinsuke TobaYoshimasa TakahashiYasuko OrbaWilliam W. HallKatsumi MaenakaHirofumi SawaAkihiko SatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kentaro Uemura Michihito Sasaki Takao Sanaki Shinsuke Toba Yoshimasa Takahashi Yasuko Orba William W. Hall Katsumi Maenaka Hirofumi Sawa Akihiko Sato MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
description	Abstract Although the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a worldwide pandemic, there are currently no virus-specific drugs that are fully effective against SARS-CoV-2. Only a limited number of human-derived cells are capable of supporting SARS-CoV-2 replication and the infectivity of SARS-CoV-2 in these cells remains poor. In contrast, monkey-derived Vero cells are highly susceptibility to infection with SARS-CoV-2, although they are not suitable for the study of antiviral effects by small molecules due to their limited capacity to metabolize drugs compared to human-derived cells. In this study, our goal was to generate a virus-susceptible human cell line that would be useful for the identification and testing of candidate drugs. Towards this end, we stably transfected human lung-derived MRC5 cells with a lentiviral vector encoding angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2. Our results revealed that SARS-CoV-2 replicates efficiently in MRC5/ACE2 cells. Furthermore, viral RNA replication and progeny virus production were significantly reduced in response to administration of the replication inhibitor, remdesivir, in MRC5/ACE2 cells compared with Vero cells. We conclude that the MRC5/ACE2 cells will be important in developing specific anti-viral therapeutics and will assist in vaccine development to combat SARS-CoV-2 infections.
format	article
author	Kentaro Uemura Michihito Sasaki Takao Sanaki Shinsuke Toba Yoshimasa Takahashi Yasuko Orba William W. Hall Katsumi Maenaka Hirofumi Sawa Akihiko Sato
author_facet	Kentaro Uemura Michihito Sasaki Takao Sanaki Shinsuke Toba Yoshimasa Takahashi Yasuko Orba William W. Hall Katsumi Maenaka Hirofumi Sawa Akihiko Sato
author_sort	Kentaro Uemura
title	MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
title_short	MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
title_full	MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
title_fullStr	MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
title_full_unstemmed	MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
title_sort	mrc5 cells engineered to express ace2 serve as a model system for the discovery of antivirals targeting sars-cov-2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2b7cd11ffa764b428313e3718883b4d1
work_keys_str_mv	AT kentarouemura mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT michihitosasaki mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT takaosanaki mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT shinsuketoba mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT yoshimasatakahashi mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT yasukoorba mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT williamwhall mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT katsumimaenaka mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT hirofumisawa mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2 AT akihikosato mrc5cellsengineeredtoexpressace2serveasamodelsystemforthediscoveryofantiviralstargetingsarscov2
_version_	1718385439021203456

MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2

Ejemplares similares