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

• Published in: Scientific reports Vol. 11; no. 1; pp. 5376 - 9
• Main Authors: Uemura, Kentaro, Sasaki, Michihito, Sanaki, Takao, Toba, Shinsuke, Takahashi, Yoshimasa, Orba, Yasuko, Hall, William W., Maenaka, Katsumi, Sawa, Hirofumi, Sato, Akihiko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326; 631/326/596; 631/326/596/1296; 631/326/596/4130; ACE2; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Antiviral drugs; Cell Engineering; Cell Line; Coronaviruses; COVID-19; COVID-19 - drug therapy; Drug development; Drug Discovery; Humanities and Social Sciences; Humans; Infectivity; Models, Biological; multidisciplinary; Pandemics; Peptidyl-dipeptidase A; Replication; Ribonucleic acid; RNA; RNA viruses; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Vaccine development; Vero cells; Viral Proteins - biosynthesis; Virus Replication - drug effects
• DOI: 10.1038/s41598-021-84882-7
• ISSN: 2045-2322

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.