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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • COVID-19 Drug Treatment
  • Cell Engineering*
  • Cell Line
  • Drug Discovery*
  • Humans
  • Models, Biological*
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / physiology*
  • Viral Proteins / biosynthesis
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Viral Proteins
  • Angiotensin-Converting Enzyme 2