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
  • 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. [email protected].
  • 11. Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan. [email protected].
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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