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-...
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2021-03-01
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doaj-2b7cd11ffa764b428313e3718883b4d12021-03-11T12:12:58ZengNature Publishing GroupScientific Reports2045-23222021-03-011111910.1038/s41598-021-84882-7MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2Kentaro Uemura0Michihito Sasaki1Takao Sanaki2Shinsuke Toba3Yoshimasa Takahashi4Yasuko Orba5William W. Hall6Katsumi Maenaka7Hirofumi Sawa8Akihiko Sato9Drug Discovery and Disease Research Laboratory, Shionogi & Co., LtdDivision of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido UniversityDrug Discovery and Disease Research Laboratory, Shionogi & Co., LtdDrug Discovery and Disease Research Laboratory, Shionogi & Co., LtdDepartment of Immunology, National Institute of Infectious DiseasesDivision of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido UniversityInternational Collaboration Unit, Research Center for Zoonosis Control, Hokkaido UniversityLaboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido UniversityDivision of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido UniversityDrug Discovery and Disease Research Laboratory, Shionogi & Co., LtdAbstract 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.https://doi.org/10.1038/s41598-021-84882-7 |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Kentaro Uemura Michihito Sasaki Takao Sanaki Shinsuke Toba Yoshimasa Takahashi Yasuko Orba William W. Hall Katsumi Maenaka Hirofumi Sawa Akihiko Sato |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-84882-7 |
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