tetano
Editor, Senior Moderator
Sci Rep
. 2021 Mar 8;11(1):5376.
doi: 10.1038/s41598-021-84882-7.
MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
Kentaro Uemura[SUP] 1 2 3 [/SUP], Michihito Sasaki[SUP] 2 [/SUP], Takao Sanaki[SUP] 1 2 [/SUP], Shinsuke Toba[SUP] 1 2 [/SUP], Yoshimasa Takahashi[SUP] 4 [/SUP], Yasuko Orba[SUP] 2 5 [/SUP], William W Hall[SUP] 5 6 7 [/SUP], Katsumi Maenaka[SUP] 3 8 9 [/SUP], Hirofumi Sawa[SUP] 2 5 7 [/SUP], Akihiko Sato[SUP] 10 11 [/SUP]
Affiliations
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.
. 2021 Mar 8;11(1):5376.
doi: 10.1038/s41598-021-84882-7.
MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
Kentaro Uemura[SUP] 1 2 3 [/SUP], Michihito Sasaki[SUP] 2 [/SUP], Takao Sanaki[SUP] 1 2 [/SUP], Shinsuke Toba[SUP] 1 2 [/SUP], Yoshimasa Takahashi[SUP] 4 [/SUP], Yasuko Orba[SUP] 2 5 [/SUP], William W Hall[SUP] 5 6 7 [/SUP], Katsumi Maenaka[SUP] 3 8 9 [/SUP], Hirofumi Sawa[SUP] 2 5 7 [/SUP], Akihiko Sato[SUP] 10 11 [/SUP]
Affiliations
- 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.