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

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

  • Sci Rep. 2021 Mar 8;11(1):5376. doi: 10.1038/s41598-021-84882-7.
Kentaro Uemura 1 2 3,  Michihito Sasaki 2,  Takao Sanaki 1 2,  Shinsuke Toba 1 2,  Yoshimasa Takahashi 4,  Yasuko Orba 2 5,  William W Hall 5 6 7,  Katsumi Maenaka 3 8 9,  Hirofumi Sawa 2 5 7,  Akihiko Sato 10 11
Affiliations

Affiliations

  • 1 Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd, Osaka, Japan.
  • 2 Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  • 3 Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  • 4 Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
  • 5 International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  • 6 National Virus Reference Laboratory, School of Medicine, University College of Dublin, Dublin, Ireland.
  • 7 Global Virus Network, Baltimore, MD, USA.
  • 8 Center for Research and Education On Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  • 9 Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo, Japan.
  • 10 Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd, Osaka, Japan. akihiko.sato@shionogi.co.jp.
  • 11 Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan. akihiko.sato@shionogi.co.jp.
PMID: 33686154 DOI: 10.1038/s41598-021-84882-7
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.

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